Endocrine Abstracts

JOINT1905

Prostate cancer (PCa) is a major cause of male cancer-related mortality worldwide, emphasising the need for non-invasive diagnostic and prognostic biomarkers and therapeutic targets for this pathology. MicroRNAs (miRNAs) have emerged as promising diagnostic and therapeutic tools for various pathologies. In this study, we investigated the microRNA landscape in plasma samples from PCa patients and explored their potential diagnostic and therapeutic value. Initially, the miRNome of plasma samples from an discovery cohort of healthy subjects (n=18) and PCa patients (n=19) was determined using an Affymetrix-miRNA array. Subsequently, the major changes were validated in an independent and ample validation cohort [n=202 (91 healthy subjects, and 111 PCa patients)] by quantitative real-time PCR. In addition, in silico and In vitro approaches were performed on normal (RWPE-1 and PNT-2) and tumour (LNCaP, DU145, and PC-3) prostate cell models. The results from the discovery cohort revealed that the expression of 104 miRNAs was significantly altered. Among these, miR-191-5p emerged as a particularly noteworthy candidate due to its potential clinical utility and its role in the pathophysiology of PCa. Specifically, miR-191-5p levels were significantly elevated in PCa patients, highlighting a potential diagnostic value particularly within the Grey Zone of PSA (range of 3 to 10 ng/mL), wherein PSA sensitivity and specificity for diagnosing PCa is limited. Notably, the diagnostic capacity of miR-191-5p was further enhanced in PCa patients with obesity (BMI>30). Then, a bioinformatics approach was employed, using diverse tools to identify potential targets regulated by miR-191-5p, which showed 13 potential oncogenic targets. Further analyses in PCa cell models in response to miR-191-5p overexpression identified TMOD2, a migration-related gene, as the most consistently decreased target. Furthermore, TMOD2 levels were also confirmed to be modulated by miR-191-5p by using a novelty miRNA-target interaction blocker. Altogether, our findings demonstrate that miR-191-5p may serve as a novel and effective personalised diagnostic biomarker in PCa, particularly among patients with obesity, and as a potential therapeutic tool worth to be explored in PCa patients.