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

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 overexpr