Abstract 3487: Identification and validation of PCAT14 as prognostic biomarker in prostate cancer

Abstract

Abstract Background: Early detection of prostate cancer, largely facilitated by the advent of PSA screening, has also been attributed to over-diagnosis and overtreatment of this disease. While stratifying patients into risk groups based on clinicopathologic features is currently used to guide treatment decisions, it is clear that current stratification approaches need to be further refined to allow better personalization of therapy. Thus, identifying molecular biomarkers to distinguish indolent versus aggressive disease would address an unmet need in the clinical management of prostate cancer. Advances in next-generation sequencing technologies have enabled thorough characterization of cancer transcriptomes, especially in unraveling the realm of non-coding RNAs (ncRNAs). In particular, lncRNAs, a class of ncRNAs, have gained increasing attention as biomarkers due to their tissue- and cancer-specific expression profile. Thus, lncRNAs may be relevant in the clinical management of prostate cancer (PCa). Methods and Results: Here we assembled and analyzed a large RNA-seq dataset, from 585 PCa 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 versus malignant cases, as well as high versus low Gleason disease. In prostate cancer cell lines, the endogenous PCAT14 levels are induced by CRISPR/SAM technique, which significantly suppresses cell invasion. Conclusion: By performing differential expression analysis between prostate cancer with low vs high Gleason scores, we identified lncRNA PCAT14 as a prostate cancer- and lineage- specific biomarker of indolent disease. We show that PCAT14 is an AR-regulated transcript and its overexpression suppresses invasion of prostate cancer cells. Moreover, in multiple independent datasets, PCAT14 expression associates with favorable outcomes in prostate cancer and adds prognostic value to standard clinicopathologic variables. Citation Format: Lanbo Xiao, Sudhanshu Shukla, Xiangy Zhang, Yashar Niknafs, Rohit Malik, Arul Chinnaiyan. Identification and validation of PCAT14 as prognostic biomarker in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3487. doi:10.1158/1538-7445.AM2017-3487