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
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.