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.

Tumor-Derived Exosomal Long Noncoding RNAs as Promising Diagnostic Biomarkers for Prostate Cancer

“…SChLAP1 increases with progression of PCa and predicts poor prognosis of patients with PCa [11, 12]. More importantly, these cancer-related lncRNAs can be detected in body fluids, such as blood and urine [13, 14], which makes them ideal diagnostic and prognostic biomarkers for cancer patients. However, previous studies focused mainly on the diagnostic value of SChLAP1 in tissue [15].…”

A Novel Analysis of the Differentiated Expression of Long Noncoding RNAs Profiles in Human Prostate Cancer

“…PCAT-14 is commonly up-regulated in primary tumors. PCAT14 is an AR-regulated transcript while PCAT14 is highly expressed in low grade disease and loss of PCAT14 predicts for disease aggressiveness and recurrence, and its overexpression suppresses invasion of PCa cells [45]. PCAT14 lower expression is signi cantly prognostic for multiple clinical endpoints supporting its signi cance for predicting metastatic disease that could be used to improve patient management [46].…”

Long Non-Coding RNA as Potential Biomarker for Prostate Cancer: Is It Making a Difference?

“…Recently, Maher’s group [79,80] has reported that an aberrant downregulation of prostate cancer associated transcript-14 (PCAT-14) was associated with Gleason score and a greater probability of metastatic progression, overall survival, and prostate cancer-specific mortality across multiple independent datasets and ethnicities. Moreover, studies in in vitro cell cultures demonstrated that a downregulation of PCAT14 increased cell migration while an overexpression reduced cell growth, migration and invasion, suggesting that PCAT14 may possess a significant biological role in PCa tumorigenesis and progression, and may function as a potential biomarker for PCa detection and prognosis.…”