Abstract C018: MicroRNA and tRNA fragments as biomarkers for prostate cancer aggressiveness in self-reported black and white men: Results of a pilot study
Authors: Kim Yeonju , Dyson Gregory , Dombkowski Alan , Dlugas Hunter , Lucas Steven , Domina Jason , Bock Cathryn 
Published: September 2024

Abstract
Prostate cancer (PC) is one of the most common cancers in men worldwide, but current risk-stratification biomarkers are limited in sensitivity and specificity. PC mortality in Black men is twice that of White men in Michigan, and in Detroit, three times greater. Recent assessments of small non-coding regulatory RNAs, including microRNAs (miR) and tRNA fragments (tRFs), as potential low-cost, non-invasive screening biomarkers have shown expression profiles that may predict PC aggressiveness across race. Thus, we conducted a pilot study evaluating miR and tRF as PC risk stratification biomarkers among self-reported African American/Black (AA) and White men. RNA from patient tissue (MRI-identified target and non-target biopsy) was extracted, sequenced, and assessed for mature human miRs and tRFs via miRbase and oncotRF. Using p-value-corrected univariate negative binomial regression, we assessed differential expression of miR and tRF across race, age at biopsy, aggressiveness (Gleason grade group 1, 2-3, 4-5), biopsy site, and cancer status (grade 1-5 vs. 0). RNA-specific gene targets implicated in PC were obtained via miRTarBase, tRFtarget, and KEGG. Among 34 patients receiving an MRI-guided biopsy (26% AA, 74% White; median age 64), 53% had cancer at MRI-indicated target sites (44% in AA, 56% in White), with 27% grade 1 (33% in AA, 24% in White), 20% grade 2-3 (11% in AA, 24% in White), and 6% grade 4-5 cancer (0% in AA, 8% in White). Multivariate analysis across all samples revealed 20 miRs with significantly increased expression in grade 4-5 vs. grade 1 cancer (p=0.001-0.042), two of which also had increased expression in grades 2-3 (p=0.026; miR-3529-3p, miR-7-5p). miR gene targets (n= 320) included PTEN (miR-130b-3p, miR-182-5p, miR-200a-3p, miR-20b-5p), CDKN1B (miR-200b-3p), and KLF6 (miR-20b-5p) associated with grade 4-5; and AR (miR-7-5p) associated with grade 2-3 cancer. Seven tRFs had increased expression in grade 2-3 vs. 1 cancer (p=0.0003-0.047). Of note, Mi-tRNA-Asp-GTC-2-1_L22_pos29 targeted KLF6, MAD1L1, and ZFHX3 genes. Nine tRFs had decreased expression in grade 2-3 vs. 1 cancer (p=0.003-0.33), of which 5-tRNA-Lys-CTT-2-1_L30, S3-mito-tRNA-Val-TAC_L22, and S5-tRNA-Gly-TCC-1-1_L30 targeted MAD1L1, RNASEL, ZFHX3, AR, EHBP1, KLF6, and PTEN. Two tRFs decreased in expression with lower age at biopsy (p=0.036-0.046). When stratified by race, two miR (miR-941, p=0.025; miR-140-5p, p=0.009) and five tRF (p=0.0003-0.037) had increased expression with positive cancer status uniquely among AA men. Of these, M5-tRNA-Glu-CTC-1-1_L23 and Mi-tRNA-Val-CAC-5-1_L20_pos56 had increased and Mi-tRNA-Val-CAC-5-1_L21_pos55 and Mi-tRNA-Asp-GTC-2-1_L23_pos51 had decreased expression in grade 2-3 vs. 1 cancer (p&lt;0.001; gene targets AR, PTEN). The small sample size precluded additional comparisons. Our pilot study revealed differential miR and tRF expression across risk and self-reported race with known PC gene targets, highlighting their potential as biomarkers for future investigation in the context of persistent racial disparities in PC outcomes.
Citation Format: Yeonju Kim, Gregory Dyson, Alan Dombkowski, Hunter Dlugas, Steven Lucas, Jason Domina, Cathryn Bock. MicroRNA and tRNA fragments as biomarkers for prostate cancer aggressiveness in self-reported black and white men: Results of a pilot study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C018.