Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer

• Published in: Neoplasia (New York, N.Y.) Vol. 18; no. 8; pp. 489 - 499
• Main Authors: Shukla, Sudhanshu, Zhang, Xiang, Niknafs, Yashar S, Xiao, Lanbo, Mehra, Rohit, Cieślik, Marcin, Ross, Ashley, Schaeffer, Edward, Malik, Bhavna, Guo, Shuling, Freier, Susan M, Bui, Huynh-Hoa, Siddiqui, Javed, Jing, Xiaojun, Cao, Xuhong, Dhanasekaran, Saravana M, Feng, Felix Y, Chinnaiyan, Arul M, Malik, Rohit
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2016; Elsevier
• Subjects: Biomarkers, Tumor; Cell Line, Tumor; Cluster Analysis; Disease Progression; Follow-Up Studies; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; In Situ Hybridization; Kaplan-Meier Estimate; Male; Neoplasm Grading; Neoplasm Recurrence, Local; Oncology; Prognosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Reproducibility of Results; RNA Transport; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism
• ISSN: 1476-5586; 1522-8002; 1476-5586
• DOI: 10.1016/j.neo.2016.07.001

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.