Abstract B36: Overexpression of PVT1 exons 4A, 4B, and 9 is characteristic of aggressive prostate cancer in males of African ancestry

Abstract

African ancestry is an established nonmodifiable risk factor for aggressive prostate cancer (PCa). The underlying biologic mechanisms are still unclear. We previously demonstrated that exon 9 of PVT1, a long nonprotein coding gene, may be involved in racial disparity in PCa. Using the most recent full-genome variability panel from the 1000 Genomes project, we recently identified a string of 75 SNPs in a 26-kb region spanning PVT1 exons 4A and 4B as consistently showing the highest level of genetic differentiation between African and non-African populations. However, the expression of PVT1 exons 4A, 4B, and 9 in prostate tissues of males of African ancestry (MoAA) has never been investigated. We aimed to determine the expression of PVT1 exons 4A, 4B, and 9 in histologically confirmed normal prostate (n=22), benign tumor prostate (n=35), and malignant tumor prostate tissue (n=28) samples obtained from males who had undergone prostatectomy or transrectal ultrasound-guided biopsy in Nigeria, a sub-Saharan Black African population. Tissues were collected in compliance with Institutional Review Board-approved protocols and histopathologic analysis was performed. RNA extraction, cDNA synthesis, and quantitative-PCR were performed to analyze mRNA expression of PVT1 exon 4A, PVT1 exon 4B, and PVT1 exon 9. There was a statistically significant difference in the expression of PVT1 exon 4A (F(2,61)=9.031, p=0.000); PVT1 exon 4B (F(2,61)=5.294, p=0.004); and PVT1 exon 9 (F(2,61)=3.700, p=0.029) between groups as determined by one-way ANOVA. Tukey post-hoc test revealed mean expression of PVT1 exon 4A = 3.15±0.49 (95% CI [2.13, 4.17]), PVT1 4B = 2.24±0.360 (CI [1.47, 2.95]), and PVT1 exon 9 = 1.644±0.95 (95% CI [1.265, 2.023]) in prostate tumor tissues. The results show an overexpression of PVT1 exon 4A, PVT1 exon 4B, and PVT1 exon 9 in malignant prostate tissue compared with nonmalignant tissue in MoAA. Also, using RNA ISH, PVT1 exon 9 was detected overexpressed primarily in the epithelium of prostate tumor tissue. In conclusion, the results also suggest that (1) the overexpression of PVT1 exon 4A, PVT1 exon 4B, and PVT1 exon 9 is characteristic of PCa in MoAA and (2) overexpression of PVT1 exon 4B and PVT1 exon 9 is specific for PCa, and that PVT1 exon 4B may distinguish between indolent and aggressive PCa in MoAA. Citation Format: Adeodat Ilboudo, Akintunde Orunmuyi, Cuong Bach, Olorunseun Ogunwobi. Overexpression of PVT1 exons 4A, 4B, and 9 is characteristic of aggressive prostate cancer in males of African ancestry [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B36.