title: Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer.
abstract: Rapid advances in the discovery of long noncoding RNAs (lncRNAs) have identified lineage- and cancer-specific biomarkers that may be relevant in the clinical management of prostate cancer (PCa). Here we assembled and analyzed a large RNA-seq dataset, from 585 patient samples, including benign prostate tissue and both localized and metastatic PCa to discover and validate differentially expressed genes associated with disease aggressiveness. We performed Sample Set Enrichment Analysis (SSEA) and identified genes associated with low versus high Gleason score in the RNA-seq database. Comparing Gleason 6 versus 9+ PCa samples, we identified 99 differentially expressed genes with variable association to Gleason grade as well as robust expression in prostate cancer. The top-ranked novel lncRNA PCAT14, exhibits both cancer and lineage specificity. On multivariate analysis, low PCAT14 expression independently predicts for BPFS (P=.00126), PSS (P=.0385), and MFS (P=.000609), with trends for OS as well (P=.056). An RNA in-situ hybridization (ISH) assay for PCAT14 distinguished benign vs malignant cases, as well as high vs low Gleason disease. PCAT14 is transcriptionally regulated by AR, and endogenous PCAT14 overexpression suppresses cell invasion. Thus, Using RNA-sequencing data we identify PCAT14, a novel prostate cancer and lineage-specific lncRNA. PCAT14 is highly expressed in low grade disease and loss of PCAT14 predicts for disease aggressiveness and recurrence.
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA.
authors: Sudhanshu
authors: S
authors: Shukla
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
authors: Xiang
authors: X
authors: Zhang
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA.
authors: Yashar S
authors: YS
authors: Niknafs
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA.
authors: Lanbo
authors: L
authors: Xiao
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA.
authors: Rohit
authors: R
authors: Mehra
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA.
authors: Marcin
authors: M
authors: Cieślik
authors: James Buchanan Brady Urological Institute, Johns Hopkins University, USA.
authors: Ashley
authors: A
authors: Ross
authors: James Buchanan Brady Urological Institute, Johns Hopkins University, USA.
authors: Edward
authors: E
authors: Schaeffer
authors: Department of Radiation Oncology, University of Michigan, Ann Arbor, USA.
authors: Bhavna
authors: B
authors: Malik
authors: Ionis Pharmaceutical, CA.
authors: Shuling
authors: S
authors: Guo
authors: Ionis Pharmaceutical, CA.
authors: Susan M
authors: SM
authors: Freier
authors: Ionis Pharmaceutical, CA.
authors: Huynh-Hoa
authors: HH
authors: Bui
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA.
authors: Javed
authors: J
authors: Siddiqui
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA.
authors: Xiaojun
authors: X
authors: Jing
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA.
authors: Xuhong
authors: X
authors: Cao
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA.
authors: Saravana M
authors: SM
authors: Dhanasekaran
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Radiation Oncology, University of Michigan, Ann Arbor, USA.
authors: Felix Y
authors: FY
authors: Feng
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, USA. Electronic address: arul@med.umich.edu.
authors: Arul M
authors: AM
authors: Chinnaiyan
authors: Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, USA; Department of Pathology, University of Michigan, Ann Arbor, USA.
authors: Rohit
authors: R
authors: Malik
mesh_terms: D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D018450:Disease Progression; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008297:Male; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D034443:RNA Transport; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding