Abstract 1915: A plasma biomarker panel of microRNAs miR-133-3p and miR-153-3p for diagnosis of prostate cancer

Abstract Prostate cancer is highly prevalent and the second-leading cause of cancer-related death among men in the United States. Its incidence rate has been rising by 3% per year overall and by about 5% per year for advanced-stage disease. Current diagnostic methods, particularly the PSA test, remain controversial due to variable sensitivity and limited specificity, highlighting the need for more precise and minimally invasive diagnostic tools. MicroRNAs (miRNAs)—19-24-nucleotide, non-coding RNAs—have emerged as critical regulators of gene expression and are frequently deregulated in cancer. These miRNAs exhibit cancer-specific dysregulation, high sensitivity, and stability, positioning them as strong candidates for blood-based biomarkers in early cancer detection and prognosis. Using computational miRNA target prediction analysis, we identified several miRNAs—namely, miR-133a/b, miR-144, miR-153, and miR-590—that could serve as highly sensitive and specific biomarkers for early prostate cancer detection. Our bioinformatics analysis further revealed that these miRNAs regulate glutathione S-transferase P1 (GSTP1), a gene often epigenetically silenced in early prostate cancer stages, suggesting their potential diagnostic value. To evaluate this, we analyzed miRNA levels in 84 human plasma samples from 56 prostate cancer patients and 28 non-cancer individuals served as controls using quantitative real-time PCR. Sensitivity and specificity were assessed through Receiver Operating Characteristic (ROC) curve analysis. The expression of miR-133-3p and miR-153-3p were significantly elevated in the plasma of prostate cancer patients compared to the control group, with p-values of 0.021 and 0.0006, respectively. Binary logistic regression and ROC analyses comparing these miRNAs to PSA showed significantly higher sensitivity and specificity, with p-values of 0.0001 and 0.0003. This two-miRNA panel exhibited near-perfect diagnostic accuracy, with an area under the curve (AUC) ranging from 0.98 to 1.0. Compared with previously identified miRNA biomarkers, this 2-miRNA panel demonstrated greater diagnostic stability and superior performance across public dataset cohorts. Our findings suggest that miR-133-3p and miR-153-3p could serve as reliable blood-based biomarkers for diagnosis of prostate cancer. Their association with GSTP1—a gene implicated in early prostate cancer through epigenetic silencing—underscores their biological relevance to the disease. The high sensitivity and specificity of this panel represent a significant improvement over PSA-based screening and indicate its promise for clinical application in prostate cancer diagnostics. Overall, this study supports the development of miRNA-based diagnostic tests to enable earlier detection, reduce unnecessary treatments, and ultimately improve outcomes for prostate cancer patients. Citation Format: Shiv Verma, Cheryl L. Thompson, Pingfu Fu, Gregory T. MacLennan, Sanjay Gupta. A plasma biomarker panel of microRNAs miR-133-3p and miR-153-3p for diagnosis of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1915.