Unraveling the Role of EV-Derived miR-150-5p in Prostate Cancer Metastasis and Its Association with High-Grade Gleason Scores: Implications for Diagnosis

SIMPLE SUMMARY: This study focuses on prostate cancer metastasis, a leading cause of patient mortality. The research explores extracellular vesicle (EV)-enclosed microRNAs as potential diagnostic tool for prostate cancer. Using microarray analysis, the study identifies distinct microRNA expression profiles in metastatic lymph nodes, primary tumor tissues, and non-metastatic lymph nodes. Notably, miR-140-3p, miR-150-5p, and miR-23b-3p exhibit differential expression. Evaluation of exosomes from plasma and cancer cells reveals low miR-150-5p expression associated with high Gleason scores, suggesting its role in Wnt pathway regulation and bone metastasis. EV-derived miR-150-5p emerges as a promising diagnostic marker for early-stage metastasis and high-grade Gleason scores. ABSTRACT: Metastasis remains the leading cause of mortality in prostate cancer patients. The presence of tumor cells in lymph nodes is an established prognostic indicator for several cancer types, such as melanoma, breast, oral, pancreatic, and cervical cancers. Emerging evidence highlights the role of microRNAs enclosed within extracellular vesicles as facilitators of molecular communication between tumors and metastatic sites in the lymph nodes. This study aims to investigate the potential diagnostic utility of EV-derived microRNAs in liquid biopsies for prostate cancer. By employing microarrays on paraffin-embedded samples, we characterized the microRNA expression profiles in metastatic lymph nodes, non-metastatic lymph nodes, and primary tumor tissues of prostate cancer. Differential expression of microRNAs was observed in metastatic lymph nodes compared to prostate tumors and non-metastatic lymph node tissues. Three microRNAs (miR-140-3p, miR-150-5p, and miR-23b-3p) were identified as differentially expressed between tissue and plasma samples. Furthermore, we evaluated the expression of these microRNAs in exosomes derived from prostate cancer cells and plasma samples. Intriguingly, high Gleason score samples exhibited the lowest expression of miR-150-5p compared to control samples. Pathway analysis suggested a potential regulatory role for miR-150-5p in the Wnt pathway and bone metastasis. Our findings suggest EV-derived miR-150-5p as a promising diagnostic marker for identifying patients with high-grade Gleason scores and detecting metastasis at an early stage.