MicroRNAs in Prostate Cancer Liquid Biopsies: Early Detection, Prognosis, and Treatment Monitoring

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, <i>miR-141</i> and <i>miR-375</i> are elevated in metastatic cases, whereas <i>let-7</i> family members and <i>miR-326</i> are upregulated in aggressive disease, highlighting their prognostic value. Moreover, dynamic changes in reported miRNAs during therapy provide real-time insights into treatment response. In androgen-deprivation therapy (ADT), oncogenic miRNAs, such as <i>miR-21</i> and <i>miR-125b</i>, increase upon resistance, whereas a decline in tumor-suppressive miRNAs, such as <i>miR-23b/-27b</i>, flags the transition to castration-resistant PCa (CRPC). Similarly, baseline levels of miRNAs (e.g., <i>miR-200b/c</i>, <i>miR-20a</i>) can predict chemotherapy outcomes. Integrating multi-miRNA panels has demonstrated superior accuracy for risk stratification and monitoring, paving the way for personalized treatment. Although promising, clinical implementation of miRNA-based assays requires further validation, standardization of protocols, and large-scale prospective studies. Harnessing circulating miRNAs could usher in a new era of precision oncology for PCa, improving early diagnosis, prognostication, and real-time therapeutic guidance.