title: Clinically-relevant cell type cross-talk identified from a lung tumor microenvironment interactome

status: Public on Jun 01 2018

city: Stanford

first: Andrew

last: Gentles

address: 1201 Welch Road

institute: Stanford University

summary: Tumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions between malignant cells and a single stromal cell type, often along a single pathway. To develop a deeper understanding of the interactions between cells within human lung tumors we performed RNA-seq profiling of flow-sorted malignant cells, endothelial cells, immune cells, fibroblasts, and bulk cells from freshly resected human primary non-small-cell lung tumors. We mapped the cell-specific differential expression of prognostically-associated secreted factors and cell surface genes, and computationally reconstructed cross-talk between these cell types to generate a novel resource we call the Lung Tumor Microenvironment Interactome (LTMI). Using this resource, we identified and validated a prognostically unfavourable influence of Gremlin-1 production by fibroblasts on proliferation of malignant lung adenocarcinoma cells. We also found a favorable association between infiltration of mast cells and less aggressive tumor cell behavior. These results illustrate the utility of the LTMI as a resource for generating hypotheses concerning tumor-microenvironment interactions that may have prognostic and therapeutic relevance.

overall_design: RNA seq profiling of sorted and unsorted populations from non-small cell lung cancer surgical biopsies.


title: Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers

status: Public on Feb 07 2018

city: Duarte

first: Crystal

middle: N

last: Marconett

email: cmarcone@usc.edu, cmarconett@coh.org

state: CA

address: 1500 E Duarte Rd

department: Integrative Translational Sciences

country: USA

institute: City of Hope

type: Expression profiling by high throughput sequencing

summary: Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P = 1.13 × 10-62) and CYP1B1 (P < 2.49 × 10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis.

overall_design: RNAseq of DMSO or cigarette smoke condensate (CSC)-treated A549 human lung adenocarcinoma cells. Cells were treated for either 48 hours or 2 weeks, as indicated.

first: Theresa

middle: R

last: Stueve

first: Wen

middle: Q

last: Li

first: Jianxin

last: Shi

first: Tongwu

last: Zhang

first: Chenchen

last: Yang

first: Daniel

middle: J

last: Mullen

first: C

last: Yan

first: William

last: Wheeler

first: Xing

last: Hua

first: Beiyun

last: Zhou

first: Zea

last: Borok

first: Neil

middle: E

last: Caporaso

first: Angela

middle: C

last: Pesatori

first: Jubao

last: Duan

first: Ite

middle: A

last: Laird-Offringa

first: Maria

middle: T

last: Landi


title: The embryo-larval and adult parts of the zebrafish major alpha/beta-globin gene locus are functionally and structurally independent

status: Public on Jul 12 2017

city: Cambridge

first: Aleksandra

last: Galitsyna

state: Massachusetts

address: 77 Massachusetts Avenue

department: IMES

institute: Massachusetts Institute of Technology

summary: We have demonstrated that, in developing Danio rerio, the embryo-larval and adult subloci of the major globin locus acquire stage-specific hyperacetylation of histone H3 and that H3 hyperacetylation profiles differ significantly between the embryo-larval sublocus (high level of acetylation within gene bodies but not in intergenic regions) and adult sublocus (extended domains of H3 acetylation covering both gene bodies and intergenic regions). The spatial organization of the two subloci is also found to be different. Whereas the adult sublocus is organized into a relatively compact contact domain, the embryo-larval sublocus has a rather low density of spatial contacts. Finally, we have demonstrated that the conserved upstream enhancer of the locus establishes spatial contacts with transcribed adult genes, but not with transcribed embryo-larval genes, and that the embryo-larval and adult subloci of the major globin gene locus are separated by an insulator colocalizing with a CTCF-binding site.

overall_design: 5C analysis of the major alpha/beta-globin gene domain in erythroid cells of Danio rerio

first: Anastasia

middle: P

last: Kovina


title: Host transcription profile in nasal epithelium and blood of hospitalized children under two years old with Respiratory Syncitial Virus infection [whole blood]

status: Public on Apr 14 2017

city: Ho Chi Minh City

first: Lien Anh Ha

last: Do

address: 764 Vo Van Kiet, Ward 1, District 5

country: Viet Nam

institute: Oxford University Clinical Research Unit, Vietnam

summary:
Analysis of transcriptional profiles in whole blood and nasopharyngeal swaps from children hospitalized with lower respiratory tract infections at their admission and their discharge, and diagnosed with either RSV or rhinovirus infections.
The hypothesis is that this information will contribute to better understand the viral specific immunity and host responses to RSV infection and may suggest leads for the develoment of vaccines and specific treatment.

overall_design: Total RNA extracted from whole blood and nasopharyngeal swaps (lysed with PreAnalyti X and Rneasy Mini kit respectively) drawn from individual pediatric patients with acute RSV and hRV acute respiratory tract infection. A total of 332 samples are analyzed in pairwise comparisons (acute versus convalescent phase for blood and nasopharyngeal swaps): 60 with hRV, 76 with acute RSV and 30 with acute RSV co-infected .

first: Lien

first: Johann

last: Pellet

first: Rogier

middle: H

last: van Doorn

first: Anh

last: Tran

first: Bach

last: Nguyen

first: Thi

first: Quynh

first: Quoc

middle: B

last: Vo

first: Nguyen

last: Dac

first: Hong

last: Trinh

first: Bao

last: Le Binh

first: Khanh

last: Le

first: Minh

first: Quang

last: Thai

first: Thanh

middle: V

first: Ngoc

last: Ngo

middle: K

last: Dang

last: Cao

first: Thu

first: Lu

last: Ho

first: Bertrand

last: De Meulder

first: Charles

last: Auffray

first: Jorrit-Jan

last: Hofstra

first: Jeremy

last: Farrar

first: Juliet

last: Bryant

first: Menno

last: de Jong

first: Martin

middle: L

last: Hibberd


title: Host transcription profile in nasal epithelium and blood of hospitalized children under two years old with Respiratory Syncitial Virus infection [nasopharyngeal swaps]

first: Lien Anh Ha

last: Do

first: Lien

first: Johann

last: Pellet

first: Rogier

last: van Doorn

first: Anh

last: Tran

first: Bach

last: Nguyen

first: Thi

first: Quynh

first: Quoc

last: Vo

first: Nguyen


title: Single cell profiling of CD4+ T cells from human fetal intestine

status: Public on Nov 24 2018

city: Leiden

last: Li

address: Albinusdreef 2

country: Netherlands

institute: LUMC

summary: The fetus is thought to be protected from exposure to foreign antigens, yet CD45RO+ T-cells reside in the fetal intestine. We combined functional assays with mass cytometry, single-cell RNA-sequencing, and high-throughput TCR-sequencing to characterize the fetal intestinal CD4+ T-cell compartment. We identified 22 CD4+ T-cell clusters, including naive-like, regulatory-like, and memory-like subpopulations, which were confirmed and further characterized at the transcriptional level. Memory-like cells expressed high levels of Ki-67, indicating cell division, and CD5, a surrogate marker of TCR-avidity, and produced IFN-γ and IL-2. Pathway analysis revealed a differentiation trajectory associated with cellular activation and proinflammatory effector functions, and TCR-repertoire analysis demonstrated clonal expansions, distinct repertoire characteristics, and interconnections between subpopulations of memory-like CD4+ T-cells. Imaging-mass cytometry further showed that memory-like CD4+ T-cells colocalized with antigen-presenting cells. Collectively, these results provided evidence for the generation of memory-like CD4+ T-cells in the human fetal intestine, consistent with exposure to foreign antigens.

overall_design: Single, live, CD3+CD8a–TCRγδ–CD4+/– T-cells from one human fetal  intestines were processed on the Chromium 3' single cell platform (10x Genomics) and sequenced on an Illumina HiSeq 4000.

first: Frits

last: Koning

first: Susan

last: Kloet


title: Endogenous Muscle Atrophy F-box is Involved in the Development of Cardiac Rupture After Myocardial Infarction

status: Public on Apr 07 2017

city: Kanazawa

first: Soichiro

last: Usui

address: 13-1 Takaramachi

department: Department of System Biology

country: Japan

institute: Kanazawa University, Graduate School of Medical Sciences

summary:
Muscle atrophy F-box (MAFbx/atrogin-1), an E3 ubiquitin ligase, is a crucial mediator of skeletal muscle atrophy and cardiac hypertrophy in response to pressure overload and exercise.
We investigated the role of MAFbx in the regulation of cardiac remodeling following MI. A DNA microarray analysis was conducted using total RNA from wild type and MAFbx KO mouse hearts subject to permanet coronary ligation. Results provide insight into the molecular mechanism to mediate the role of MAFbx upon cardiac remodeling after myocardial infarction

overall_design: We applied permanet coronary ligation of left coronary artery to wild type and MAFbx KO mice, and extracted total RNA one day after surgery. The gene expression profiles were examined by Affymetrix Mouse Gene ST Array.

first: Akio

last: Chikata

first: Shin-ichiro

last: Takashima

first: Ayano

last: Nomura

first: Daniela

last: Zablocki

first: Shuichi

last: Kaneko

first: Junichi

last: Sadoshima

first: Masayuki

last: Takamura


title: Transcriptomic comparison between nickel hyperaccumulator and non-accumulator plant species from the Leucocroton and Lasiocroton genus (Euphorbiaceae)  from Cuba

status: Public on Jun 05 2019

city: Auzeville Tolosane

first: Sylvain

last: MERLOT

address: 24, chemin de Borde Rouge

department: Biological Sciences

country: France

institute: CNRS

summary: The leaf transcriptome of the nickel hyperaccumulator Leucocroton havanensis (Euphorbiaceae) living on serpentine Cuabal,  from  Cuba, was compared to the closely related non-accumulator Lasiocroton microphyllus living on Gallery forest on limestone soil, to identity differentially expressed genes potentially involved in Ni hyperaccumulation.

sample_organism:
Lasiocroton microphyllus
Leucocroton havanensis

overall_design: Leaves from independent plants of  Leucocroton havanensis and Lasiocroton micrphyllus  were collected in their natural environment.  Leucocroton havanensis  was also in vitro cultured on Murashige & Skoog medium with agar containing 500 mg/L NiSO4 as described in Gonzalez, D. & Matrella, S. Nickel hyperaccumulation ‘in vitro’ by Leucocroton havanensis (Euphorbiaceae). Rev. del Jardín Botánico Nac. 34–35, 83–88 (2013). RNA of the 3 independant samples were extracted and sequenced using the Illumina paired-end sequencing technology. Reads from Leucocroton havanensis in vitro cultured experiment and Lasiocroton microphyllus environmental sample were assembled de novo to generate transcriptome sequences. The transcriptome of L. havanensis was used as a reference to compare the expression of genes in the three samples.

first: Dubiel

last: Gonzalez

first: Vanesa

middle: S

last: Garcia de la Torre

first: Ludivine

last: Soubigou-Taconnat

last: Merlot

first: Rosalina

last: Berazaín


title: Pleiotropic Analysis of Lung Cancer and Blood Triglycerides

status: Public on Nov 06 2016

first: Crystal

last: Marconett

type: Methylation profiling by high throughput sequencing

summary: Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10-6) and blood triglycerides (P = 1.39x10-5). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10-4) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21, Pcombined = 5.20x10-9). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer.

overall_design: Whole genome bisulfite sequencing of purified human primary AT2 cells from remnant transplant lungs of 2 donors.

first: Verena

last: Zuber

first: Jianxin

last: Shi

first: Xing

last: Hua

first: William

last: Wheeler

first: Chenchen

last: Yang

first: Lei

last: Song

first: Anders

middle: M

last: Dale

first: Mariana

last: Laplana

first: Angela

last: Risch

first: Aree

last: Witoelar

first: Wesley

last: Thompson

first: Andrew

last: Schork

first: Francesco

last: Betella

first: Yunpeng

last: Wang

first: Srdjan

last: Djurovic

first: Beiyun

last: Zhou

first: Zea

last: Borok

first: Henricus

middle: F

last: van der Heijden

first: Jacqueline

last: de Graff

first: Dorine

last: Swinkels

first: Katja

last: Aben

first: James

last: McKay

first: Rayjean

last: Hung

first: Heike

last: Bikeboller

first: Victoria

last: Stevens

first: Demetrius

last: Albanes

first: Neil

last: Caporaso

first: Younghun

last: Han

first: Yongyue

last: Wei

first: Maria

last: Panadero

first: Jose

middle: I

last: Mayordomo

first: David

last: Christiani

first: Lambertus

last: Kiemeney

first: Ole

last: Andreassen

first: Richard

last: Houlston

first: Christopher

last: Amos

first: Nilanjan


title: Cross-species transcriptome profiling identifies new alveolar epithelial type I cell-specific genes

status: Public on Nov 03 2016

first: Crystal

middle: N

last: Marconett

summary: Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells. To address this, we performed genome-wide expression profiling of multiple rat organs alongside purified rat AT2, AT1 and in vitro differentiated AT1-like cells, resulting in identification of 54 candidate AT1 cell markers. Cross-referencing with genes upregulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes.  Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as unique to AT1 cells, while SCNN1G within lung is restricted to AT1 cells. RNAseq confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence of mouse alveoli verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells. These new AT1 cell-specific genes, with GRAMD2 as a leading candidate, will enhance AT1 cell isolation, investigation of alveolar epithelial cell differentiation potential, and contribution of AT1 cells to distal lung diseases.

overall_design: RNAseq of purified primary human alveolar epithelial type 2 (AT2) and in vitro differentiated type 1 (AT1-like) cells.

first: Beiyun

last: Zhou

first: Mitsuhiro

last: Sunohara

first: Tiffany

last: Pouldar

first: HongJun

last: Wang

first: Yixin

last: Liu

first: Megan

last: Rieger

first: Evelyn

last: Tran

first: Per

last: Flodby

first: Kimberly

middle: D

last: Siegmund

first: Edward

last: Crandall

first: Ite

last: Laird-Offringa

first: Zea

last: Borok


title: Sarcoma Classification by DNA-methylation profiling

status: Public on Mar 01 2020

city: Heidelberg

first: Daniel

last: Schrimpf

address: Im Neuenheimer Feld 224

department: Neuropathology

country: Germany

institute: University Hospital Heidelberg, Intitute of Pathology

summary: DNA methylation classification reference set (1077) and validation set (428) of  1505 sarcoma samples using Illumina HumanMethylation450 BeadChips or  Illumina Infinium HumanMethylation850 BeadChips


title: A crucial function for c-Kit(+) in cardiac regeneration: role of Wnt inhibition

status: Public on Nov 30 2016

city: Durham

first: Conrad

last: Hodgkinson

state: NC

address: 210 Research Dr, GSRBII, Box 3718

institute: Duke University

summary: Purpose: To explore the effects of Wnt inhibitor Sfrp2 and to clarify the changes that in situ c-Kit(+) cells undergo in the infarcted heart we performed transcript profiling (RNA-seq)

overall_design:
Methods: Eight week C57BL6 c-KitCreERT2/mTeG mice were injected for 14 consecutive days with tamoxifen (0.5 mg/day by i.p) to induce Cre expression and to label c-Kit(+) cells with eGFP. Mice underwent MI and two days later were treated with vehicle or Sfrp2. C-Kit(+) cells were isolated one day prior to MI, one day post-MI and 12 days post-MI (vehicle and Sfrp2). Cardiac biopsies were isolated for c-Kit(+) cells. Total RNA from the purified c-Kit(+) population was isolated using a PicoPure Arcturus kit (Invitrogen). Complimentary cDNA was generated with an Ovation Pico WTA System V2 kit (NuGEN). RNA-seq was performed with 2 lanes on a HiSeq 2000 instrument yielding a total of >400,000,000 PF clusters. Gene Ontology analysis was performed by the Duke Genomic Core. RNA-seq data was processed using the TrimGalore toolkit which employs Cutadapt to trim low quality bases and Illumina sequencing adaptors from the 3’ end of the reads. Only reads that were 20nt or longer after trimming were kept for further analysis. Reads were mapped to the GRCm38v68 version of the mouse genome and transcriptome using the STAR RNA-seq alignment tool. Reads were kept for further analysis if they mapped to a single genomic location. Gene counts were compiled using the HTseq tool. Only genes that had at least 10 reads in any given library were used in subsequent analysis. Normalization and differential expression was carried out using the DESeq2 Bioconductor package with the R statistical programming environment. The false discovery rate was calculated to control for multiple hypothesis testing. Gene set enrichment analysis was performed to identify differentially regulated pathways and gene ontology terms for each of the comparisons performed.
Results: Sfrp2 promotes the differentiation of c-Kit(+) cells into cardiomyocyte-like cells

first: Victor

last: Dzau


title: Cross-species transcriptome profiling identifies new alveolar epithelial type I cell-specific genes

summary: Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed lineage tracing studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells. In this study, we performed genome-wide expression profiling of multiple rat organs alongside purified rat AT2, AT1 and in vitro differentiated AT1-like cells, resulting in identification of 54 candidate AT1 cell markers. Cross-referencing with genes upregulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes.  Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as highly specific to AT1 cells. RNAseq confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells and is not expressed in bronchial epithelial cells, while RT-PCR confirmed that it is not expressed in endothelial cells. Utilizing GRAMD2 as a new AT1 cell-specific gene will enhance AT1 cell isolation, investigation of alveolar epithelial cell differentiation potential, and contribution of AT1 cells to distal lung diseases.

overall_design: Two preps of purified AT1 cells  (92%, and 93% pure, respectively) were isolated from Sprague-Dawley male rats and RNA was extracted using Trizol. In addition, RNA was extracted from bronchoalveolar lavage cells and 14 rat tissues: kidney, spleen, ileum, duodenum, colon, stomach, skin, brain, testis, skeletal muscle, trachea, heart, salivary gland, and liver.


title: GRP78 regulates ER homeostasis and distal epithelial cell survival during lung development

status: Public on Jan 15 2016

summary: Bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, has been linked to endoplasmic reticulum (ER) stress. To investigate a causal role for ER stress in BPD pathogenesis, we generated mice (cGrp78f/f) with lung epithelial cell-specific knockout (KO) of Grp78, a gene encoding the ER chaperone 78-kDa glucose-regulated protein (GRP78), a master regulator of ER homeostasis and the unfolded protein response (UPR). Lung epithelial-specific Grp78 KO disrupted lung morphogenesis, causing developmental arrest, increased alveolar epithelial type II cell apoptosis and decreased surfactant protein and type I cell marker expression in perinatal lungs. cGrp78f/f pups died immediately after birth, likely due to respiratory distress. Importantly, Grp78 KO triggered UPR activation with marked induction of pro-apoptotic transcription factor C/EBP homologous protein (CHOP). Increased expression of genes involved in oxidative stress and cell death and decreased expression of genes encoding antioxidant enzymes suggest a role for oxidative stress in alveolar epithelial cell (AEC) apoptosis. Increased Smad3 phosphorylation and expression of transforming growth factor-β (TGF-β)/Smad3 targets Cdkn1a (encoding p21) and Gadd45a suggest that interactions among the apoptotic arm of the UPR, oxidative stress and TGF-β/Smad signaling pathways contribute to Grp78 KO-induced AEC apoptosis and developmental arrest. Chemical chaperone taursodeoxycholic acid reduced UPR activation and apoptosis in cGrp78f/f lungs cultured ex vivo, confirming a role for ER stress in observed AEC abnormalities. These results demonstrate a key role for GRP78 in AEC survival and gene expression during lung development through modulation of ER stress and suggest the UPR as a potential therapeutic target in BPD.

overall_design: Whole-genome expression profiling was performed using MouseRef-8 v2.0 Expression BeadChips (Illumina) on RNA isolated from lungs of four Grp78f/f and three cGrp78f/f mice at E18.

first: Changgong

last: Li

first: Hongjun

first: Parviz

last: Minoo

first: Amy

last: Lee


title: mRNA and miRNA expression profiles for fresh frozen periampullary adenocarcinomas (pancreatobiliary and intestinal type) and adjacent normal tissues. [mRNA]

status: Public on Nov 06 2015

city: Oslo

first: Vandana

last: Sandhu

state: oslo

address: Ullernchausseen 70

department: Department of Genetics

country: Norway

institute: Radiumhospitalet, Oslo

summary: To study the molecular signatures of mRNAs and miRNAs which can potentially act as a prognostic biomarkers in pancreatobiliary and intestinal types of periampullary adenocarcinomas

overall_design: Total RNA was isolated from 10 x 20 µm sections of 81 fresh frozen tumor samples for mRNA  expression profiling. A total of 49 PDAC, 8 bile duct adenocarcinoma, 8 ampulla of pancreatobiliary tye, 7 ampulla of intestinal type, 9 duodenum sample and 12 adjacent normal samples were used. These samples were analysed by microarray analysis using the 60K agilent platform. The expression profiles were background corrected and quantile normalized for mRNA. Filtering of controls, unannotated genes and low expressed probes was done.

first: Elin

last: Kure


title: mRNA and miRNA expression profiles for fresh frozen periampullary adenocarcinomas (pancreatobiliary and intestinal type) and adjacent normal tissues.

type:
Expression profiling by array
Non-coding RNA profiling by array

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Molecular profile of ketamine in comparison to memantine and phencyclidyne and other psychotropic drugs

status: Public on Dec 31 2015

city: Krakow

first: Marcin

last: Piechota

address: Smetna 12

department: Molecular Neuropharmacology

country: Poland

institute: Institute of Pharmacology PAS


title: Molecular profile of ketamine in comparison to memantine and phencyclidyne and other psychotropic drugs [mouse striatum]

summary:
Ketamine has been found to elicit a rapid antidepressant effects in treatment-refractory affective disorders. To indicate the underlying mechanism of action we have performed whole-genome microarray profiling. Moreover, the effects of ketamine were compared to other NMDA receptor antagonists phencyclidine and memantine.
Type: Drug response, Time-course, Gene expression profiling with Illumina Microarrays
Keywords: Ketamine, NMDA antagonist, Phencyclidyne, Memantine, Time-course, Gene Expression, Acute treatment

overall_design: The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse striatum. Three NMDA antagonists (ketamine 20 mg/kg, phencyclidine 5 mg/kg and memantine 15 mg/kg i.p.) were selected for the comparison. Drug doses were based on the literature. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naive animals were prepared for each time point. Samples from 2 mice were pooled per microarray, 3 biological replicates were used per time point and 12 arrays per each drug. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches.  'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.

first: M

last: Korostynski


title: Epigenome analysis of leukemia stem, blast and normal hematopoietic stem/progenitor cells

status: Public on Oct 01 2015

city: Baltimore

first: Andrew

last: Feinberg

state: MD

address: 855 N. Wolfe St., Rangos 570

department: Medicine

institute: Johns Hopkins University

summary: Genome wide DNA methylation profiling of leukemia stem, blast cells obtained from 15 AML patients and of normal hematopoietic stem/progenitor cells from 5 normal bone marrow. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in the samples. Samples included 20 leukemia stem cells, 24 blast cells and 30 normal hematopoietic stem and progenitor cells (6 different types from 5 normal bone marrows).

overall_design: Bisulphite converted DNA from the 74 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: Namyoung

last: Jung


title: Molecular profile of ketamine in comparison to memantine and phencyclidyne and other psychotropic drugs [mouse hippocampus]

overall_design: The microarray experiment was performed to analyze time-course of drug-induced transcriptional response in C57BL/6J mouse hippocampus. Three NMDA antagonists (ketamine 20 mg/kg, phencyclidine 5 mg/kg and memantine 15 mg/kg i.p.) were selected for the comparison. Drug doses were based on the literature. To analyze dynamics of early, intermediate and relatively late changes of mRNA abundance the experiment was performed in four time points (1, 2, 4 and 8h after drug administration). To exclude influence of drug injection and circadian rhythm on gene expression profile, control groups of saline treated and naive animals were prepared for each time point. Samples from 2 mice were pooled per microarray, 3 biological replicates were used per time point and 12 arrays per each drug. To provide appropriate balance in the whole dataset groups were equally divided between the array hybridization batches.  'Complete' normalized data and non-normalized data (containing control rows not represented in Platform GPL6105) are linked below as supplementary files.


title: Genome-wide analysis of gene expression of ascending aorta from patients with acute Stanford type A aortic dissection

status: Public on Dec 31 2014

city: Shanghai

first: Sun

last: Pan

address: Fenglin Road 180

department: Department of Cardiac Surgery

country: China

institute: Zhongshan Hospital, Fudan University

summary: Differentially expressed genes were identified by comparing the gene expression profiling of dissected ascending aorta with that of control. Results provide important information to indicate pathogenesis of aortic dissection.

overall_design: Total RNA obtained from dissected ascending aorta compared to normal ascending aorta.


title: Prospective gene expression analysis of  human RNA samples from Hepatocellular Carcinoma in relation with growth rate and survival

status: Public on Jan 22 2014

city: Modena

first: Erica

last: Villa

address: Via del Pozzo 71

country: Italy

institute: University of Modena and Reggio Emilia

summary: The aim of this study is to identify  by  whole genome microarray  expression profiling a molecular  signature of HCC samples that correlates with growth rate of the tumor and survival. This signature could eventually be used as prognostic marker. The samples were prospectively derived from hepatocellular carcinoma tissue as well as non-tumor tissue from the livers of the same patients.  Expression of five genes (ANGPT2, NETO2,NR4A1,DLL4,ESM1) from this signature was re-evaluated in  a validation cohort by real-time PCR, confirming its correlation with growth rate and survival.

overall_design: The bioinformatical analysis of 161 microarray datasets were obtained from single color hybridization of human RNAs on Agilent Whole Human Genome Oligo Microarrays after T7 RNA  amplification. For the purpose of this study, two discriminatory gene sets analysis were performed: up-regulated and down regulated in fast-growing tumors. For the discrimination between fast- and slow-growing tumors, the fastest quartile of the growth rate spectrum was compared with the three other quartiles. For a gene to be included, a significant discrimination (uncorrected p-value <0.01) and a 2-fold expression difference was required.

first: Rosina

last: Critelli

first: Barbara

last: Lei

first: Guido

last: Marzocchi

first: Calogero

last: Cammà

first: Gianluigi

last: Giannelli

first: Patrizia

last: Pontisso

first: Stefano

last: Colopi

first: Cristian

last: Caporali

first: Giuseppe

last: Cabibbo

first: Fabiola

last: Milosa

first: Livia

last: Maccio

first: Maria

last: Martinez-Chantar

first: Paola

last: Todesca

first: Elena

last: Turola

first: Annalisa

last: Berselli

first: Nicola

last: De Maria

last: Ballestri

first: Filippo

last: Schepis

last: Loria

first: Giorgio

last: Gerunda

first: Luisa

last: Losi

first: Fabrizio

last: Di Benedetto

first: Umberto

last: Cillo


title: Knockout mice reveal key roles for claudin-18 in alveolar fluid homeostasis.

status: Public on Apr 06 2014

first: Crystal

last: Marconett

summary: Claudin proteins are major constituents of epithelial and endothelial tight junctions (TJ), where they serve as regulators of paracellular permeability to ions and solutes. Claudin-18, a member of the large claudin family, is highly expressed in lung epithelium. To elucidate the role of claudin-18 in alveolar epithelial barrier function and fluid homeostasis, we generated claudin-18 knockout (C18 KO) mice. Increased alveolar fluid clearance (AFC) observed in C18 KO mice may have accounted for absence of lung edema despite increased alveolar solute permeability compared to wild type (WT) controls. Higher AFC in C18 KO mice was associated with higher Na-K-ATPase activity and increased expression of the Na-K-ATPase β1 subunit compared to WT controls. Consistent with in vivo findings, alveolar epithelial cell (AEC) monolayers derived from C18 KO mice exhibited lower transepithelial electrical resistance (RT) accompanied by increased solute and ion permeability without changes in ion selectivity. Expression of claudin-3 and claudin-4 was markedly increased in whole lung and in freshly isolated AEC from C18 KO mice, while claudin-5 was unchanged. In contrast, occludin, another major component of the TJ complex, was significantly decreased in C18 KO lung. Further analysis revealed rearrangements in the F-actin cytoskeleton in C18 KO MAECM. These findings demonstrate a crucial non-redundant role for claudin-18 in regulation of alveolar epithelial tight junction composition and permeability to ions and solutes.  Importantly, increased AFC in C18 KO mice identifies additional roles for claudin-18 in alveolar fluid homeostasis beyond its direct contributions to barrier properties of the alveolar epithelium.

overall_design: Animals with a ubiquitous knockout (C18 KO) were obtained by crossing mice harboring a conditional (floxed) allele of claudin-18 (Cldn18F/F) with CMV-cre deleter mice to delete exons 2 and 3 by Cre/loxP recombination.

first: Guanglei

last: Li

first: Per

last: Flodby

first: Jiao

last: Luo

first: Hidenori

last: Kage

first: Arnold

last: Sipos

first: Danping

last: Gao

first: LaMonta

last: Beard

first: Lucas

last: DeMaio

first: Yong

last: Kim

first: Kwang-Jin

first: Ite

last: Laird-Offringa

first: Parviz

last: Minoo

first: Janice

last: Liebler

first: Beiyun

last: Zhou

first: Edward

last: Crandall

first: Zea

last: Borok


title: Heterogeneity of gene-expression profiles of hepatocellular carcinoma tumors

status: Public on Mar 25 2014

city: Dallas

first: Yujin

last: Hoshida

state: TX

address: 5323 Harry Hines Blvd

institute: University of Texas Southwestern Medical Center

summary: BACKGROUND & AIMS: In approximately 70% of patients with hepatocellular carcinoma (HCC) treated by resection or ablation, disease recurs within 5 years. Although gene expression signatures have been associated with outcome, there is no method to predict recurrence based on combined clinical, pathology, and genomic data (from tumor and cirrhotic tissue). We evaluated gene expression signatures associated with outcome in a large cohort of patients with early stage (Barcelona-Clinic Liver Cancer 0/A), single-nodule HCC and heterogeneity of signatures within tumor tissues.  METHODS: We assessed 287 HCC patients undergoing resection and tested genome-wide expression platforms using tumor (n = 287) and adjacent nontumor, cirrhotic tissue (n = 226). We evaluated gene expression signatures with reported prognostic ability generated from tumor or cirrhotic tissue in 18 and 4 reports, respectively. In 15 additional patients, we profiled samples from the center and periphery of the tumor, to determine stability of signatures. Data analysis included Cox modeling and random survival forests to identify independent predictors of tumor recurrence.  RESULTS: Gene expression signatures that were associated with aggressive HCC were clustered, as well as those associated with tumors of progenitor cell origin and those from nontumor, adjacent, cirrhotic tissues. On multivariate analysis, the tumor-associated signature G3-proliferation (hazard ratio [HR], 1.75; P = .003) and an adjacent poor-survival signature (HR, 1.74; P = .004) were independent predictors of HCC recurrence, along with satellites (HR, 1.66; P = .04). Samples from different sites in the same tumor nodule were reproducibly classified.  CONCLUSIONS: We developed a composite prognostic model for HCC recurrence, based on gene expression patterns in tumor and adjacent tissues. These signatures predict early and overall recurrence in patients with HCC, and complement findings from clinical and pathology analyses.

overall_design: Center and peripheral portions of hepatocellular carcinoma tumors as well as surrounding non-tumor cirrhotic liver tissues were obtained from fresh frozen surgically resected tissues, and isolated total RNA samples were analyzed for genome-wide expression profiles.


title: Integrated transcriptomic and epigenomic analysis of primary human lung cell differentiation (ChIP-Seq)

status: Public on Apr 15 2013

first: Crystal

last: Marconett

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Analysis of chromatin state during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), and Day 8 in culture (AT1-like cells).

overall_design: Examination of 2 different histone modifications in 2 cell types.

first: Megan

last: Rieger

first: Suhaida

last: Selamat

first: Mickael

last: Dubourd

first: Sean

last: Lynch

first: Kimberly

last: Siegmund

first: Benjamin

last: Berman


title: Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes of local and large-scale chromatin spatial structure

status: Public on Jul 12 2017

first: Aleksandra

last: Galitsyna

summary: We have analyzed the total transcription output, the overall chromatin contact profile, and CTCF binding within the 2.7 Mb segment of chicken chromosome 14 harboring the alpha-globin gene cluster in cultured lymphoid cells and cultured erythroid cells before and after induction of terminal erythroid differentiation. We found that, similarly to mammalian genome, the chicken genome is organized in TADs and compartments. Full activation of the alpha-globin gene transcription in differentiated erythroid cells is correlated with upregulation of several adjacent housekeeping genes and the emergence of abundant intergenic transcription. An extended chromosome region encompassing the alpha-globin cluster becomes significantly decompacted in differentiated erythroid cells, and depleted in CTCF binding and CTCF-anchored chromatin loops, while the sub-TAD harboring alpha-globin gene cluster and the upstream regulatory element (MRE) becomes highly enriched with chromatin interactions as compared to lymphoid and proliferating erythroid cells. The alpha-globin gene domain and the neighboring loci reside within the A-like chromatin compartment in both lymphoid and erythroid cells and become further segregated from the upstream gene desert upon terminal erythroid differentiation.

overall_design: 5C and C-TALE analysis of chromatin spatial structure and total rRNA-depleted transcriptome sequencing in three chicken cultured cell lines

first: Sergey

last: Ulianov


title: Human CD14+CD16- and CD16+ monocyte-derived macrophages primed by GM-CSF or M-CSF

status: Public on Apr 21 2015

city: Mexico City

first: Carmen

last: Sánchez-Torres

department: Molecular Biomedicine

country: Mexico

institute: CINVESTAV-IPN

summary: Identification of genes differentially expressed between human CD14+CD16- and CD16+ monocyte-derived macrophages generated in the presence of either GM-CSF (termed GM14 and GM16, respectively) or M-CSF (termed M14 and M16, respectively)

overall_design: Human peripheral  CD14+CD16- and CD16+ blood monocytes from three independent healthy donors (D1, D2 and D3) were isolated by positive selection from peripheral blood mononuclear cells (PBMC) using magnetic separation systems (MACS, Miltenyi Biotec). Briefly, PBMC were first incubated with MACS anti-CD56 antibody conjugated to paramagnetic microbeads in order to eliminate the NK (CD16+) cell fraction. NK-depleted PBMC were further incubated with MACS anti-CD16 antibody to isolate CD16+ monocytes. CD56-CD16- PBMC were finally incubated with MACS anti-CD14 antibody to obtain the CD14+CD16- monocyte fraction. Monocytes were cultured for 7 days in medium containing either GM-CSF or M-CSF. Total RNA from each condition was extracted using the RNeasy kit (Qiagen) and hybridized to an Agilent Human Whole Genome (4x44) Oligo Microarray. All experimental procedures were performed following manufacturer instructions.

last: Sanchez-Torres

first: Angel

last: Corbi


title: Endogenous expression of an oncogenic PI3K mutation leads to activated PI3K pathway signaling and an invasive phenotype

status: Public on Aug 10 2011

city: South San Francisco

first: Peter

last: Haverty

address: 1 DNA Way

department: Bioinformatics

institute: Genentech, Inc.

summary:
The PTEN/PI3K pathway is commonly mutated in cancer and therefore represents a rational target for therapeutic intervention. In order to investigate the primary phenotype(s) mediated by mutant PIK3CA in a clean and highly patient-relevant context, we utilized a non-tumorigenic MCF10A parental and isogenic knock-in cell line that harbors a common activating PIK3CA kinase domain mutation (H1047R). We found that introduction of an endogenously mutated PIK3CA primarily results in a marked epithelial-mesenchymal transition (EMT) and invasive phenotype compared to isogenic wild-type cells.  Moreover, a potent and selective inhibitor of PIK3CA (GDC-0941) was highly effective and selective on reversing this phenotype compared to cell-proliferation, highlighting a potential new paradigm for studying PI3K-pathway targeted agents.

Keywords: Expression Array

overall_design: Gene expression profiles from a parental MCF10A breast line and an MCF10A clone that has a PI3K activating mutation (H1047R) knocked-in. We plated the cells in 10cm dishes overnight in media with serum, but lacking EGF or insulin. DMSO or GDC-0941 (PI3K inhibitor) at an EC50 concentration were added to triplicate plates of cells in the morning. After 4 hours the RNA was harvested using the Qiagen RNeasy kit.  There are 12 samples total.

first: Jeff

last: Wallin

first: Jane

last: Guan

first: Zora

last: Modrusan

first: Sabrina

last: Arena

first: Evelyn

last: Yao

first: Klaus

last: Hoeflich

first: Alberto

last: Bardelli

first: Christopher

last: Torrance

first: Marcia

last: Belvin

first: Lori

last: Friedman


title: Two distinct auto-regulatory loops operate at the Pu.1 locus in B cells and myeloid cells

status: Public on Feb 21 2011

city: Birmingham

first: Salam

middle: Adli

last: Assi

address: IBR

department: Institute for Cancer and Genomic Sciences

country: United Kingdom

institute: University of Birmingham

summary: The transcription factor PU.1 occupies a central role in controlling myeloid and early B cell development and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis-element (URE) whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the URE alone is insufficient to confer physiological PU.1 expression, but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays and detailed molecular analyses we present evidence that Pu.1 is regulated by a novel mechanism involving cross-talk between different cis-elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell-type specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements.

overall_design: Two DNaseI hypersensitivity datasets; bone marrow derived-macrophages and Splenic CD19+IgM+ B cells were used to study PU.1 regulatory elements

first: Mathias

last: Leddin

first: Chiara

last: Perrod

first: Maarten

last: Hoogenkamp

first: Saeed

last: Ghani

first: Sven

last: Heinz

first: Nicola

last: Wilson

first: George

last: Follows

first: Jörg

last: Schönheit

first: Lena

last: Vockentanz

first: Ali

last: Mosamam

first: Wei

last: Chen

first: Daniel

middle: G

last: Tenen

first: David

middle: R

last: Westhead

first: Berthold

last: Göttgens

first: Constanze

last: Bonifer

first: Frank

last: Rosenbauer


title: Integrated transcriptomic and epigenomic analysis of primary human lung cell differentiation (Rat)

city: Duarte

first: Crystal

last: Marconett

institute: City of Hope

summary: Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), Days 2, 4, and 6 in culture (differentiating) and Day 8 in culture (AT1-like cells).

overall_design:
1ug of RNA was subjected to cRNA conversion using Illumina TotalPrep RNA kit and hybridized to the HT12v4 array
Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells

first: Beiyun

last: Zhou

first: Megan

last: Rieger

first: Suhaida

middle: A

last: Selamat

first: Mickael

last: Dubourd

first: Sean

last: Lynch

first: Kimberly

last: Siegmund

first: Benjamin

last: Berman

first: Zea

last: Borok

first: Ite

last: Laird-Offringa


status: Public on Feb 17 2011

first: Yujin

last: Hoshida

summary: Gene-expression profiles of formalin-fixed, paraffin-embedded human hepatocellular carcinoma tissues obtained at the time of surgical resection.

overall_design: Gene-expression profiling was performed using formalin-fixed, paraffin-embedded hepatocellular carcinoma tissues obtained at the time of surgical resection.

first: Augusto

last: Villaneuva

first: Josep

last: Llovet

first: Todd

last: Golub


title: mRNA expression profile in IMR-90 cells in response to TGF-β1

status: Public on Aug 07 2009

first: Victor

middle: John

last: Thannickal

state: AL

address: 1530 3rd Avenue South, THT 422

institute: University of Alabama at Birmingham

summary: Members of the NADPH oxidase (NOX) family of enzymes, which catalyze the reduction of O2 to reactive oxygen species, have increased in number during eukaryotic evolution. Seven isoforms of the NOX gene family have been identified in mammals; however, specific roles of NOX enzymes in mammalian physiology and pathophysiology have not been fully elucidated. The best established physiological role of NOX enzymes is in host defense against pathogen invasion in diverse species, including plants. The prototypical member of this family, NOX-2 (gp91phox), is expressed in phagocytic cells and mediates microbicidal activities. Here we report a role for the NOX4 isoform in tissue repair functions of myofibroblasts and fibrogenesis. Transforming growth factor-β1 (TGF-β1) induces NOX-4 expression in lung mesenchymal cells by a SMAD-3–dependent mechanism. NOX-4–dependent generation of hydrogen peroxide (H2O2) is required for TGF-β1–induced myofibroblast differentiation, extracellular matrix (ECM) production and contractility. NOX-4 is upregulated in lungs of mice subjected to noninfectious injury and in cases of human idiopathic pulmonary fibrosis (IPF). Genetic or pharmacologic targeting of NOX-4 abrogates fibrogenesis in two murine models of lung injury. These studies support a function for NOX4 in tissue fibrogenesis and provide proof of concept for therapeutic targeting of NOX-4 in recalcitrant fibrotic disorders.

overall_design: mRNA expression of genes in human fetal lung mesenchymal cells (IMR-90) treated with or without TGF-β1, as analyzed by Affymetrix (U133A) microarrays.  Control (C0, C2, C3) = cells without TGF-β1 treatment (n=3).  Experimental (T0, T5, T7) = cells treated with TGF-β1 (2ng/ml) (n=3).   mRNA was collected for all 6 samples for 48 hours post treatment.

middle: J

first: Louise

last: Hecker


title: Study of gene expression of human liver Hepatocellular carcinoma

status: Public on Jul 05 2011

city: Boston

first: Chunsheng

last: Zhang

address: 33 Avenue Louis Pasteur

institute: Merck

summary: Hepatocellular carcinoma (HCC) affects millions of people worldwide and is a lethal malignancy for which there are no effective therapies. To identify prognostic gene markers for liver cancer, we conducted transcriptome profiling of frozen tissues (tumor and non-tumor) from 300 early-to-advanced stage HCCs plus 40 cirrhotic and 6 normal livers.

overall_design: We have profiles 268 HCC tumor, 243 adjacent non-tumor, 40 cirrhotic and 6 healthy liver samples.


title: Array-based profiling of the lymphoma cell DNA methylome does not unequivocally distinguish primary lymphomas of the central nervous system from non-CNS diffuse large B-cell lymphomas

status: Public on Oct 01 2019

city: Ulm

first: Julia

last: Vogt

address: Albert-Einstein Allee 11

department: Institute of Human Genetics

institute: Ulm University

type: Methylation profiling by genome tiling array

summary: Genome wide DNA methylation profiling of 26 primary central nervous system lymphomas (PCNSL). The Illumina Infinium HumanMethylation 450 BeadChip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in PCNSL samples.

overall_design:
Bisulphite converted DNA from 26 PCNSL samples were hybridized to the Illumina Infinium HumanMethylation450 BeadChip.
This dataset also includes the re-analysis of existing GEO Samples (see Average_Betas_re-analyzed_detpval0.01.txt, at the foot of this record).

first: Reiner

last: Siebert


title: Gene expression study in hepatocellular carcinoma

status: Public on Jun 18 2010

city: Daejeon

first: Seon-Kyu

last: Kim

address: 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Korea

department: Personalized Genomic Medicine Research Center

country: South Korea

institute: Korea Research Institutue of Bioscience & Biotechnology

summary: Gene expression data from 100 human hepatocellular carcinomas (HCC) were generated and analyzed as part of effort for validating prognostic gene expression signatures from previous studies. Using four different classification algorithms and leave-one-out cross-validation approaches, four different prognostic signatures were applied to test the robustness and concordance of predicted outcome in individual patients.  All four tumor-derived signatures were significantly associated with prognosis and had a high rate of concordance with predicted outcomes for individual patients.

overall_design: Total RNA was extracted from the fresh frozen tissues of 100 HCC. Five-hundred nanograms of total RNA were used for labeling and hybridization, according to the manufacturer’s protocols (Illumina). After the bead chips were scanned with an Illumina BeadArray Reader (Illumina), the microarray data were normalized using the quantile normalization method in the Linear Models for Microarray Data package in the R language environment.   The expression level of each gene was transformed into a log 2 base before further analysis.

first: SH

last: Leem

first: DG

first: YJ

first: SK

first: IS

last: Chu


title: Gene Signature to Identify Vascular Invasion in Hepatocellular Carcinoma

status: Public on Jul 31 2011

summary:
Background: The presence of vascular invasion (VI) in pathology specimens has been widely described as closely linked to poor outcome in hepatocellular carcinoma (HCC) patients after tumor resection. Previous attempts have been conducted to achieve molecular markers or signatures to predict HCC recurrence in HCC. Here, we aim to develop a diagnostic model combining clinical and genomic variables able to detect the presence of VI prior to surgery and link it to survival estimation.
Methods: Seventy-nine HCV related HCC samples from patients that underwent surgical resection as a treatment for HCC were subjected to Genome-wide gene expression profiling and a predictive model of vascular invasion was constructed. The model was tested in an independent-validation set of 153 fixed tissue samples of resected HCC. Quantitative RTPCR and inmunohistochemistry were performed in HCC samples to test a potential biomarker.
Results: A 39-gene signature was able to accurately (72%) identify vascular invasion in HCC patients treated with resection. A model including tumor size and the signature is able to predict presence of VI with 85% accuracy in HCV-related HCC patients, and is able to exclude VI in up to 87% cases in HCC from all etiologies.
Conclusions: Using the VI gene signature together with tumor size, VI can be successfully detected in HCC patients. The diagnostic model, integrated in a previously reported survival chart is able to provide an estimated survival for selected cases. Clinical implications of this fact are relevant to provide objective data to further apply expanded indication of curative treatments in HCC.

first: Beatriz

last: Mínguez

last: Villanueva

first: Sara

last: Toffanin

first: Laia

last: Cabellos

first: Swan

last: Thung

first: John

last: Mandeli

first: Anja

last: Lachenmayer

first: Radoslav

last: Savic

first: Sasan

last: Roayaie

first: Craig

last: April

first: Jian-Bing

last: Fan

first: Vincenzo

last: Mazzaferro

first: Jordi

last: Bruix

first: Myron

last: Schwartz

first: Scott

last: Friedman


title: Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive HCC

status: Public on Apr 14 2010

city: Chapel Hill

first: Ivan

last: Rusyn

address: 0031 Michael Hooker Research Center

department: Gillings School of Global Public Health

institute: University of North Carolina

summary:
Background/Aims: Recurrence-free survival (RFS) following curative resection of hepatocellular carcinoma (HCC) in subjects with hepatitis C virus (HCV) infection is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized therapy. The goal of this study was to create a gene expression predictor of HCC recurrence in subjects with HCV.

Methods: Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS.

Results: The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGF-beta1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses.

Conclusions: Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression signature of the predictor gives important insights into the pathobiology of HCC recurrence and used in design of the individualized therapy.

overall_design:
43 tumor (JT) and 44 non-tumor (JNT) liver tissues surgically resected from patients with HCV-associated hepatocellular carcinoma; 8 non-tumor liver tissues (control samples, JC) surgically resected from HCV- or HBV-free patients with metastatic liver tumor.
Inter-batch normalization was carried out using Distance Weighted Discrimination procedure.

The supplementary file 'GSE17856_Readme.txt' contains a description of the replicates used for normalization. The 'GSE17856_US14702406_2514850*' files are the raw data files for the replicates.

first: Masato

last: Tsuchiya

first: Joel

last: Parker

first: Hiroshi

last: Kono

first: Masanori

last: Matsuda

first: Hideki

last: Fujii


title: Identification of cholangiocarcinoma-like gene expression traits in hepatocellular carcinoma

status: Public on May 21 2010

city: Suwon

first: Hyun Goo

last: Woo

address: 164 Worldcup-ro, Yeongtong-gu

institute: Ajou University School of Medicine

summary: We performed gene expression profiling of hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and mixed type of combined HCC and CC (CHC). In comparison of the profiles, a novel class of HCC expressing CC-like traits was identified.

overall_design: Gene expression profiling of 70 hepatocellular carcinoma (HCC), 13 cholangiocarcinoma (CC), and 7 mixed type of combined HCC and CC (CHC) were performed.

first: Hyun

first: Jeong-Hoon

last: Lee

first: Jung-Hwan

last: Yoon

first: Chung

middle: Y

last: Kim

first: Hyo-Suk

first: Ja

last: Jang

first: Nam-Joon

last: Yi

first: Kyung-Suk

last: Suh

first: Kuhn

middle: U

first: Eun

last: Park

first: Snorri

last: Thorgeirsson

first: Yoon


title: Gender differences in PAX and PAX-GRP samples

status: Public on Apr 30 2007

city: Bonn

first: Joachim

last: Schultze

address: Carl-Troll-Str. 31

department: LIMES Institute

institute: University of Bonn

summary:
The use of peripheral blood mononuclear cells (PBMC) for transcriptome analysis has already been proven valuable for assessing disease-associated and drug response related gene signatures. While these proof-of-principle studies have been critically important, the instability of RNA within PBMC prohibits their use in large scale multi-center trials for which samples have to be transported for a prolonged time prior RNA isolation. Therefore, a prerequisite for transcriptome analysis of peripheral blood in clinical trials will be a standardized and valid method to immediately stabilize the RNA profile after blood withdrawal.  We demonstrate that the globin mRNA reduction method results in significantly improved data quality of stabilized RNA samples resulting in low intra-group variance and a detection rate of expressed genes similar to PBMC. More important, even small differences in gene expression such as observed between females and males were detected and sufficient to predict gender in whole blood samples.
Keywords: biological replicates

overall_design:
Whole blood was drawn from 7 female and 7 male subjects into PAXgeneTM blood collection tubes. After isolation of total RNA, a subset of each RNA sample was subjected to  a globin reduction protocol (GRP) Microarray analysis was performed from PAX and GRP samples using Affymetrix U133A arrays.
Gene expression profiles of females and males were compared in the PAX and  the GRP group.

first: Svenja

last: Debey


title: Integrated transcriptomic and epigenomic analysis of primary human lung cell differentiation (Human)

first: Crystal

last: Marconett

address: 1500 E Duarte Rd

first: Ite

last: Laird-Offringa


title: Integrated transcriptomic and epigenomic analysis of primary human lung cell differentiation

summary: This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus

overall_design: Refer to individual Series


title: CCDC50 promotes tumor growth through regulation of lysosome homeostasis

status: Public on Dec 06 2021

city: Philadelphia

first: Tian

last: Tian

state: PA

address: 3615 Civic Center Blvd

department: Center of Applied Genomics

institute: Children's Hospital of Philadelphia

summary: Cutaneous melanoma is characterized by lineage-specific lysosome-associated vesicular trafficking. Specifically, we report a melanoma enrichened lysophagy receptor, CCDC50, controlling lysosomal homeostasis and autolysosomal activity. We reveal that targeting CCDC50 in melanoma may be a promising therapeutic strategy, as nearly 70% of human melanomas highly express CCDC50. Moreover, targeting CCDC50 together with BRAFV600E inhibition induces synergistic function in regression of melanoma tumors, representing an alternative strategy for melanoma therapy. We performed transcriptome profiling (RNA-seq) and quantitative reverse transcription polymerase chain reaction (qRT–PCR) in shCtrl and shCCDC50 cells to evaluate the melanoma growth and metastasis controlled by CCDC50. The deep sequencing results showed that CCDC50 defciency caused increased lysosome and vacuolar memebrane and blocked autophagy flux.

overall_design: A375 cells were transduced with lentivirus carring shCtrl or shCCDC50 plasmids. The infected cells were selected with puromycin for 7 days. The deletion of CCDC50 was confirmed by qRT-PCR and immunobloting. The shCtrl and shCCDC50 cells were collected for mRNA profilling analysis.

first: Deyin

last: Guo

first: Panpan

last: Hou


title: Expression data from AML cell lines

status: Public on Jul 29 2014

city: Cambridge

first: Shih-Min

last: Huang

state: MA

address: 640 Memorial Drive

department: Discovery and Early Development

institute: Sanofi Oncology

summary: Post-chemotherapy relapse presents a major unmet medical need in AML where treatment options are limited. We used gene expression profile from 32 AML cell lines to characterize expression difference between responder and non-responders to PIM inhibitors. Our results highlight the importance of STAT5 and MYC in rendering cancer cells sensitive to PIM inhibitors.

overall_design: All AML cell lines were purchased from either ATCC or DSMZ and cultured accordingly to vendors’ protocols. Gene expression were measured from the cell lines using Affymetrix microarrays. Response to PIM inhibitors (IC50) was recorded for each cell line, and association between drug response and gene expression were analyzed.

first: Guo

last: Zhuyan