Circulating miRNAs as Potential Biomarkers in Prostate Cancer Patients Undergoing Radiotherapy

Stefanos Kachris,1 Chara Papadaki,2 Konstantinos Rounis,3 Eliza Tsitoura,4 Chrysanthi Kokkinaki,4 Christoforos Nikolaou,5– 7 George Sourvinos,4 Dimitrios Mavroudis2,3 1Department of Radiation Oncology, University General Hospital, Heraklion, Crete, Greece; 2Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Crete, Greece; 3Department of Medical Oncology, University General Hospital, Heraklion, Crete, Greece; 4Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, Crete, Greece; 5Department of Biology, University of Crete, Heraklion, Crete, Greece; 6Institute of Molecular Biology and Biotechnology (IMBB), Foundation of Research and Technology (FORTH), Heraklion, Crete, Greece; 7Institute of Bioinnovation, Biomedical Science Research Center “Alexander Fleming”, Athens, GreeceCorrespondence: Dimitrios MavroudisLaboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, 71110, GreeceTel +30 2810392750Email mavroudis@uoc.grIntroduction: Disease recurrence is a major concern in patients with localized prostate cancer (PCa) following treatment with radiotherapy (RT), and few studies have evaluated the clinical relevance of microRNAs (miRNAs) prior and post-RT.Purpose: We aimed to investigate the significance of miRNAs in the outcomes of prostate cancer patients undergoing radiotherapy and to identify the related pathways through bioinformatics analysis.Materials and Methods: The expression levels of miR-21, miR-106b, miR-141 and miR-375 involved in the response to radiotherapy were assessed by RT-qPCR in the serum of PCa patients (n=56) prior- and post-RT.Results: Low expression levels of miR-106b prior-RT were associated with extracapsular extension and seminal vesicles invasion by the tumor (p=0.031 and 0.044, respectively). In the high-risk subgroup (n=47), post-RT expression levels of miR-21 were higher in patients with biochemical relapse (BR) compared to non-relapse (p=0.043). Also, in the salvage treatment subgroup (post-operative BR; n=20), post-RT expression levels of miR-21 and miR-106b were higher in patients with BR compared to non-relapse (p=0.043 and p=0.032, respectively). In the whole group of patients, high expression levels of miR-21 prior-RT and of miR-106b post-RT were associated with significantly shorter overall survival (OS; p=0.049 and p=0.050, respectively). No associations were observed among miR-141 and miR-375 expression levels with clinicopathological features or treatment outcome. Bioinformatics analysis revealed significant enrichment in DNA damage response pathways.Conclusion: Circulating miRNAs prior or post-RT may hold prognostic implications in patients with PCa.Keywords: prostate cancer, radiotherapy, salvage radiotherapy, circulating microRNAs, high risk, biochemical relaps