Abstract 471: Attenuation of circulating miR-17-5p, miR-20b-5p, and miR-106a-5p in low-risk prostate cancer patients following proton therapy

Abstract Introduction: Liquid biopsies offer a novel approach to diagnose, predict cancer outcomes, and monitor treatment response by analyzing tumor-derived substances. Circulating cell-free microRNAs (miRNAs) show clinical promise as biomarkers within prostate cancer (PCa) and have been implicated with PCa prognosis and outcomes. However, their potential for monitoring and assessing radiotherapy (RT) treatment response remains understudied. Understanding miRNA expression changes during RT is crucial, as they impact RT efficacy by directly affecting genes and proteins within RT-response pathways. Aim: This study aimed to profile the expression of three oncogenes, miR-17-5p, miR-20b-5p, and miR-106a-5p and to determine their association with PCa risk groups in patients receiving proton therapy (PT). Patients and Methods: Plasma was obtained from the University of Florida Health Proton Therapy Institute Outcomes Tracking Protocol biobank. Plasma was collected from men diagnosed with localized PCa without metastatic disease at three time points: prior to PT (PRE-PT), at 4 weeks following the start of PT (4WKSPD1), and at 8 weeks following the start of PT (8WKSPD1). The pilot study consisted of 38 patients, with 23 categorized as low-risk and 15 categorized as high-risk for PCa. MiRNA expression levels were evaluated using reverse transcription-polymerase chain reaction and quantified using the Livak method. Results: The study revealed a downregulation of miR-17-5p in response to PT, with median gene expression levels decreasing from 0. 73 at PRE-PT to 0. 587 at 8WKSPD1. Low-risk PCa patients also showed distinct miRNA expression changes with all three miRNAs (miR-17-5p, miR-20b-5p, and miR-106a-5p) downregulated from 0. 953, 1. 037, and 1. 010 at PRE-PT to 0. 398, 0. 216, and 0. 298 at 8WKSPD1, respectively. Statistical analysis using a Kruskal-Wallis test followed by a Dunn's post-hoc test identified significant differences (p=0. 035) specifically between PRE-PT and 8WKSPD1 for miR-17-5p. Conclusion: The study revealed that PT led to a time-dependent reduction in miRNA levels, indicating a higher responsiveness in low-risk compared to high-risk PCa patients. This differential response highlights miR-17-5p, miR-20b-5p, and miR-106a-5p as potential PT response biomarkers, with clinical implications for personalizing PCa treatment. These results underscore the necessity for further validation of these miRNAs to maximize their clinical utility. Citation Format: Johnny Velasquez, Curtis Bryant, Nancy Mendenhall, Luisel Ricks-Santi. Attenuation of circulating miR-17-5p, miR-20b-5p, and miR-106a-5p in low-risk prostate cancer patients following proton therapy abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 471.