The loss of the tumour-suppressor miR-145 results in the shorter disease-free survival of prostate cancer patients

• Published in: British journal of cancer Vol. 108; no. 12; pp. 2573 - 2581
• Main Authors: Avgeris, M, Stravodimos, K, Fragoulis, E G, Scorilas, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.06.2013; Nature Publishing Group
• Subjects: 631/337/384/331; 692/699/67/589/466; 692/700/1750/1976; Adult; Aged; Aged, 80 and over; Antigens; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell cycle; Disease Progression; Disease-Free Survival; Drug Resistance; Epidemiology; Gene expression; Gene Expression Regulation, Neoplastic; Gene Silencing - physiology; Genes, Tumor Suppressor - physiology; Humans; Hyperplasia; Male; Medical research; Medical sciences; MicroRNAs; MicroRNAs - genetics; MicroRNAs - physiology; Middle Aged; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nephrology. Urinary tract diseases; Oncology; Prognosis; Prostate cancer; Prostatectomy - methods; Prostatic Hyperplasia - diagnosis; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - mortality; Prostatic Hyperplasia - surgery; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - mortality; Prostatic Neoplasms - surgery; Survival Analysis; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Greece; Athens Greece; molecular tumour markers; prostate cancer; risk stratification; disease-free survival; miR-145; p53; Human; Urinary system disease; Prostate disease; Genetic marker; Risk; Tumoral marker; Malignant tumor; Molecular marker; Cancerology; TP53 Gene; Risk factor; Male genital diseases; Prostate cancer; Disease free survival; Cancer; Tumor suppressor gene
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.250

Background: Prostate cancer (PCa) is characterised by great heterogeneity of the disease progression rate. Tumours range from insignificant and not life threatening to high risk for relapse ones. Consequently, a large number of patients undergo unnecessary treatment. miR-145 is a well-documented tumour suppressor and its expression, which is regulated by the p53 pathway, has been found to be decreased in the majority of human malignancies. The aim of our study was to evaluate the clinical utility of miR-145 for the prognostication of PCa. Methods: Total RNA was isolated from 137 prostate tissue specimens obtained from 73 radical prostatectomy-treated PCa patients and 64 transurethral- or open prostatectomy-treated benign prostate hyperplasia (BPH) patients. Following polyadenylation and reverse transcription, miR-145 levels were determined by quantitative real-time PCR assay, using SNORD48 (RNU48) for normalisation purposes. Results: Downregulated miR-145 expression was found in PCa compared with BPH patients. The reduction of miR-145 expression in PCa was correlated with higher Gleason score, advanced clinical stage, larger tumour diameter and higher prostate-specific antigen (PSA) and follow-up PSA levels. In addition, higher risk for biochemical recurrence and significantly shorter disease-free survival (DFS) was found for the PCa patients expressing lower miR-145. Focusing on ‘low- and intermediate-recurrence risk’ PCa patients, miR-145 loss was revealed to be a reliable predictor of biochemical relapse and poor DFS independent from Gleason score, clinical stage, PSA and patients’ age. Conclusion: The loss of the tumour-suppressor miR-145 increases the risk for disease progression and predicts the poor survival of PCa patients.