RNA expression markers with differential expression by race/ancestry are associated with prostate tumor aggressiveness among African American men

Abstract There is growing evidence of molecular differences in prostate tumors by race or ancestry, which may contribute to the disproportionate burden of aggressive prostate cancer for African American men. Here we investigated whether RNA expression of 310 genes or non-coding RNAs that have shown differential expression (p<0.05) in prostate tumors by race/ancestry in past studies were associated with prostate tumor aggressiveness among African American men. We accessed formalin-fixed, paraffin-embedded prostate tumor tissue for 191 African American men with prostate cancer who underwent radical prostatectomy at the University of Maryland Medical Center from 1992-2021, as well as paired normal prostate tissue for a subset of the men (n=105). We generated RNA expression data using the ThermoFisher Human Clariom D array. Using Wilcoxon tests, we compared prostate tumor RNA expression by tumor aggressiveness (total Gleason score, GS, >=7 vs. <=6). The Benjamini-Hochberg False Discovery Rate approach was used to adjust for multiple comparisons. Of the 310 genes/non-coding RNAs, 110 were significantly associated with GS (p<0.05), and 65 remained significant after multiple comparison adjustment (q<0.05). Almost all (60/65) of the top findings tended to have lower expression in higher- vs. lower-grade tumors. There were several findings with q<0.01, which included B-cell CLL/lymphoma 2 (BCL2; median and IQR for GS<=6: 4.6, 4.3-4.8 and GS>=7: 4.3, 4.0-4.5; p=9.90E-05; q=0.01) and zinc finger homeobox 3 (ZFHX3; median and IQR for GS<=6: 4.0, 3.7-4.7 and GS>=7: 3.7, 3.5-4.0; p=1.30E-04; q=0.01). Notably, both genes were found to have lower expression in prostate tumor tissue in African American men compared to European American men in previous studies. Therefore, the direction of our findings with GS (lower expression for higher-grade tumors) is consistent with a potential role of these genes in prostate cancer disparities. The genes that had higher expression in higher- vs. lower-grade tumors in our study included several genes that have shown higher expression in tumor tissue from African American men than European American men in previous studies. These included splicing factor 1 (SF1; median and IQR for GS<=6: 3.5, 3.1-5.1 and GS>=7: 4.6, 3.3-7.4; p=5.60E-03; q=0.04), uroplakin 3B-like (UPK3BL; median and IQR for GS<=6: 6.1, 4.9-7.7 and GS>=7: 7.4, 5.5-9.3; p=7.20E-03; q= 0.04), and RNA binding motif protein 6 (RBM6; median and IQR for GS<=6: 9.6, 8.2-10.7 and GS>=7: 10.3, 8.9-12.1; p=0.01; q=0.05). While replication is needed, these findings add to growing evidence that RNA expression differences in prostate tumors by race or ancestry may contribute to prostate tumor aggressiveness and prostate cancer disparities. Citation Format: Jessica Yau, Ebuka Onyenobi, Yuji Zhang, Teklu B. Legesse, Gary Rose, Guangjing Zhu, Allen Burke, Ashley Cellini, Kimberly Clark, Nicholas Ambulos, Jing Yin, Søren M. Bentzen, Arif Hussain, Joanne Dorgan, Lorelei A. Mucci, Kathryn Hughes Barry. RNA expression markers with differential expression by race/ancestry are associated with prostate tumor aggressiveness among African American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1897.