Abstract 3507: PVT1 exons 4A, 4B, and 9 are overexpressed in aggressive prostate cancer, and PVT1 exon 4B may distinguish between indolent and aggressive prostate cancer
Authors: Akintunde T. Orunmuyi, Adeodat Ilboudo, Olabiyi G. Ogun, Cuong Bach, S A. Adebayo, Ayo A. Salako, E Oluwabunmi Olapade-Olaopa, Olorunseun O. Ogunwobi
Journal: Cancer Research (2017)

Abstract Aggressive prostate cancer (PCa) disproportionately affects males of African ancestry (MoAA). However, the underlying molecular mechanisms are unclear. Chromosome 8q24 is a PCa susceptibility locus that harbors the PVT1 non-coding gene. We previously demonstrated that PVT1 exon 9 may be involved in aggressive PCa. Moreover, 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 MoAA has never been investigated. Our aim was to determine the expression of PVT1 exons 4A, 4B, and 9 in histologically confirmed normal prostate (n=7), benign prostate (n=11) and malignant prostate tissue (n=11) from prostatectomy or transrectal ultrasound-guided biopsies in Nigeria, a sub-Saharan Black African population. Nine patients had tumor tissues with Gleason score ≥ 8. Tissues were collected in compliance with Institutional Ethics Board approved protocols. RNA extraction, cDNA synthesis, and quantitative-PCR were performed to analyze mRNA expression of PVT1 exons 4A, 4B, and 9. There was a statistically significant difference in the relative expression of PVT1 exons 4A (F(2,82)=9.031, p = 0.000), 4B (F(2,82)=5.294, p = 0.007) and 9 (F(2,82)=4.788, p = 0.011) between groups as determined by one-way ANOVA. Tukey posthoc test showed statistically significant differences between relative mean expression of PVT1 exons 4A, 4B and 9 in prostate tumor tissues versus normal prostate tissues: PVT1 exon 4A (prostate tumor: 3.15±0.497, 95% CI [2.13, 4.17]), (benign prostate: 1.74±0.163, 95% CI [1.41,2.07]), and (normal prostate: 1.28±0.141, 95% CI [0.989, 1.57]); PVT1 exon 4B (prostate tumor: 2.217±0.360, 95% CI[1.47, 2.95]), (benign prostate: 1.17±0.176, 95% CI [0.821,1.53]), and (normal prostate: 1.25±0.169, 95% CI [0.900, 1.60]); PVT1 exon 9 (prostate tumor: 1.71±0.190, 95% CI [1.32, 2.10]), (benign prostate: 1.26±0.148, 95% CI [.967,1.57]), and (normal prostate: 0.944±0.151, 95% CI[0.630, 1.25]). Paired t-test showed a significant difference in the expression profile for PVT1 exon 4B in prostate tumors with Gleason score ≥8 (2.98±0.539, 95% CI [1.90,4.06]) as compared to those with Gleason score ≤7 (1.32±0.340, 95% CI [0.645,2.07]) with p =0.009. These results show that overexpression of PVT1 exons 4A, 4B and 9 is characteristic of PCa in MoAA. Further, PVT1 exons 4B and 9 overexpression are specific for PCa, and PVT1 exon 4B may distinguish between indolent and aggressive PCa in MoAA. Citation Format: Akintunde T. Orunmuyi, Adeodat Ilboudo, Olabiyi G. Ogun, Cuong Bach, S A. Adebayo, Ayo A. Salako, E Oluwabunmi Olapade-Olaopa, Olorunseun O. Ogunwobi. PVT1 exons 4A, 4B, and 9 are overexpressed in aggressive prostate cancer, and PVT1 exon 4B may distinguish between indolent and aggressive 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 3507. doi:10.1158/1538-7445.AM2017-3507