Introduction: Prostate cancer (CaP) affects 1 in 7 men throughout their life time. One of the major risk factors for the development of CaP is race/ethnicity. African American (AA) men have significantly higher incidence and mortality from CaP compared to Caucasian American (CA). Our laboratory and others have recently described that cancer driver genes, including ERG and PTEN, have significantly different frequencies in AA versus CA CaP. In recent years progress has been made in evaluating the expression and role of long noncoding RNAs (lncRNAs) in prostate tumorigenesis, but variations in lncRNAs expression across race/ethnicity (AA vs CA) remains poorly understood. The objective of this study is to compare the expression of CaP related lncRNAs among AA and CA men.
Methods: Whole-mounted prostate sections from 30 patients, 15 AA and 15 CA matched for age, Gleason score and pathologic stage, were evaluated for the expression of lncRNAs that have been reported to be associated with CaP or other cancers. Probe sets were designed for the following 20 lncRNAs: CTBP1-AS, PCA3, PRNCR1, Hoxa11as, H19, HOTTIP, MEG3, PCGEM1, ST7OT1, SChLAP1, ANRIL/p15AS/CDK2BAS, HOTAIR, SRA-1/SRA, MALAT1/NEAT2, GAS5/SNHG2, PlncRNA-1/CBR3-AS1, Xist, hY1/RNY1, hY3/RNY3, PCAT-1. Tumor and benign epithelium was dissected under microscope from the slides, and the isolated RNA, passing BioAnalyzer quality control, was evaluated by using Nanostring platform. PCGEM1 expression analysis was updated in an existing QRT-PCR dataset of 88 patients (24 AA and 64 CA).
Results: Copy numbers of each gene, normalized to ten housekeeping genes, was compared between tumor and matched normal prostate epithelium and across ethnic groups. We have identified a panel of lncRNAs (CTBP1-AS, PCA3, PCAT-1, PRNCR1) overexpressed in tumor versus matched normal samples in 95% of patients when combined. Three genes were significantly downregulated in CaP (MEG3, HOTTIP, H19). Most significantly, PCGEM1 had robust overexpression in prostate tumors (over 10-fold upregulation) only in AA patients (7 of 15) but not in CAs (0 of 15), which was in concordance with evaluation of PCGEM1 in existing dataset, underscoring selective overexpression in AA CaP.
Conclusions: PCGEM1 was robustly overexpressed only in AA patients, whereas several lncRNAs were overexpressed (CTBP1-AS, PCA3, PCAT-1, PRNCR1) or downregulated (MEG3, HOTTIP, H19) in tumors of both AA and CA patients. Biomarker potential and biological functions of PCGEM1 are under further investigation.
Citation Format: Jocelyn Lee, Muhammad Jamal, Wusheng Yan, Denise young, Yingjie Song, Yongmei Chen, Shilpa Katta, Lakshmi Ravindranath, Alagarsamy Srinivasan, Jennifer Cullen, Jacob Kagan, Sudhir Srivastava, Albert Dobi, Inger L. Rosner, David G. McLeod, Isabell A. Sesterhenn, Shiv Srivastava, Gyorgy Petrovics. Increased expression of PCGEM1 lncRNA in prostate cancer of African American men. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A35.