RNAs, especially non-coding RNAs (ncRNAs), are crucial players in regulating cellular mechanisms due to their ability to interact with and regulate other molecules. Altered expression patterns of ncRNAs have been observed in prostate cancer (PCa), contributing to the disease's initiation, progression, and treatment response. This study aimed to evaluate the ability of a specific set of RNAs, including long ncRNAs (lncRNAs), microRNAs (miRNAs), and mRNAs, to discriminate between PCa and the non-neoplastic condition benign prostatic hyperplasia (BPH). After selecting by literature mining the most relevant RNAs differentially expressed in biofluids from PCa patients, we evaluated their discriminatory power in samples of unfiltered urine from 50 PCa and 50 BPH patients using both real-time PCR and droplet digital PCR (ddPCR). Additionally, we also optimized a protocol for urine sample manipulation and RNA extraction. This two-way validation study allowed us to establish that miRNAs (i.e., miR-27b-3p, miR-574-3p, miR-30a-5p, and miR-125b-5p) are more efficient biomarkers for PCa compared to long RNAs (mRNAs and lncRNAs) (e.g., PCA3, PCAT18, and KLK3), as their dysregulation was consistently reported in the whole urine of patients with PCa compared to those with BPH in a statistically significant manner regardless of the quantification methodology performed. Moreover, a significant increase in diagnostic performance was observed when molecular signatures composed of different miRNAs were considered. Hence, the abovementioned circulating ncRNAs represent excellent potential non-invasive biomarkers in urine capable of effectively distinguishing individuals with PCa from those with BPH, potentially reducing cancer overdiagnosis.
International journal of molecular sciences. 2024 Sep 19*** epublish ***
Michele Stella, Giorgio Ivan Russo, Rosario Leonardi, Daniela Carcò, Giuseppe Gattuso, Luca Falzone, Carmen Ferrara, Angela Caponnetto, Rosalia Battaglia, Massimo Libra, Davide Barbagallo, Cinzia Di Pietro, Salvatore Pernagallo, Cristina Barbagallo, Marco Ragusa
Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "G. Sichel", University of Catania, 95123 Catania, Italy., Department of Urology, Polyclinic Hospital, University of Catania, 95123 Catania, Italy., Casa di Cura Musumeci GECAS, 95030 Gravina di Catania, Italy., Istituto Oncologico del Mediterraneo, 95029 Viagrande, Italy., Department of Biomedical and Biotechnological Sciences, Oncologic, Clinical and General Pathology Section, University of Catania, 95123 Catania, Italy., DESTINA Genomica S.L., Health Sciences Technology Park (PTS), Av. de la Innovación 1, Building Business Innovation Center (BIC), 18016 Granada, Spain.