Abstract B33: miR-1207-3p, a novel biomarker of aggressive prostate cancer, displays differential expression in Caucasian men versus men of African ancestry (2016)

Abstract Prostate cancer (PCA) is frequently diagnosed in men in the western world and microRNAs (miRNAs) have been found to be dysregulated in PCA. Furthermore, the incidence and mortality of PCA are higher in men of African ancestry (moAA) than in Caucasian males (CM). Yet, there is currently no biomarker available that effectively predicts PCA outcome, while providing an explanation for the disproportionately higher burden of aggressive PCA in moAA. The discovery of a miRNA biomarker that is capable of distinguishing between indolent and aggressive PCA and displays differential expression in men of different ancestry would be important for the development and optimization of personalized treatment approaches. This study investigated the clinical significance of miR-1207-3p in PCA and determined if it contributes to explaining the disproportionate aggressiveness of PCA in moAA. In a human clinical study, we analyzed miR-1207-3p expression in PCA tissues collected from 404 patients with primary PCA. Total RNA was extracted using superscript IV first-strand synthesis system and measured by using UV spectrophotometer NanoDrop 2000. RNA samples from the 404 patients were analyzed by real-time quantitative reverse transcription polymerase chain reaction (qPCR) to examine the mRNA expression levels of miR-1207-3p. We discovered that miR-1207-3p overexpression positively correlated with overall death and PCA-specific death in patients with PCA. miR-1207-3p expression in PCA cases that resulted in overall death (7.05±4.37 versus 4.44.18±3.09, P=0.0001) or PCA-specific death (7.38±4.02 versus 4.48±3.08, P=0.0001) is significantly higher than PCA cases that remained alive. Furthermore, miR-1207-3p is overexpressed in recurrent versus non-recurrent PCA (6.53±3.75 versus 4.49±3.54). Also, we observed that miR-1207-3p was significantly overexpressed in patients with a Gleason score ≥8 (6.33±4.30) versus those ≤6 (4.81±3.40, P=&lt;0.0001). The same positive correlation with advanced disease held true for PCA stage (stage 1-2: 4.84±3.34 versus stage 3-4: 6.51±4.44 P=&lt;0.0001) and prostate-specific antigen (PSA) levels (PSA levels &lt;4: 3.97±3.79 versus PSA levels &gt;10: 5.73±3.58, P=0.002). This is the first description of miR-1207-3p as a prognostic biomarker in human clinical PCA. Interestingly, we discovered that miR-1207-3p expression in PCA patients was different between CM and moAA. qPCR analysis confirmed that miR-1207-3p expression was significantly less in PCA tissues of moAA in comparison to the PCA tissues of CM (3.00±2.65 versus 5.36±3.76, P=0.016). These findings suggest that in PCA, miR-1207-3p has the potential to be used as a prognostic biomarker and target for new therapeutics. Moreover, it may explain the disproportionately large burden of PCA on moAA. Citation Format: Dibash K. Das, Joseph R. Osborne, Jong Y. Park, Olorunseun O. Ogunwobi. miR-1207-3p, a novel biomarker of aggressive prostate cancer, displays differential expression in Caucasian men versus men of African ancestry. [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 B33.