title: The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer.
abstract: Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer.
authors.affiliation: Applied Cellular and Molecular Biology PhD Program, Agricultural and Forestry Sciences Faculty. Universidad de La Frontera, Temuco, 4811230, Chile; Creative BioScience, Santiago, 8580702, Chile.
authors.forename: Carolina
authors.initials: C
authors.lastname: Bizama
authors.forename: Felipe
authors.initials: F
authors.lastname: Benavente
authors.forename: Edgardo
authors.initials: E
authors.lastname: Salvatierra
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez-Moraga
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Espinoza
authors.forename: Elmer A
authors.initials: EA
authors.lastname: Fernández
authors.forename: Iván
authors.initials: I
authors.lastname: Roa
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Sagredo
authors.forename: Manuel
authors.initials: M
authors.lastname: Gidekel
authors.forename: Osvaldo L
authors.initials: OL
authors.lastname: Podhajcer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D064211:Connectin / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D013382:Subtraction Technique; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D064211:Connectin; D004268:DNA-Binding Proteins; D007797:Laminin; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C577285:TTN protein, human; C095567:laminin alpha 3; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein
keywords: CTBP1 and chemotherapy sensitization; gastric cancer; low-abundance transcriptome; novel biomarkers and therapeutic targets; specific intracellular pathways