Emerging role of secreted miR-210-3p as potential biomarker for clear cell Renal Cell Carcinoma metastasis

Article type: Research Article

Authors: Petrozza, Vincenzo^{a; 1} | Costantini, Manuela^{b; 1} | Tito, Claudia^{d; 1} | Giammusso, Laura Maria^c | Sorrentino, Veronica^a | Cacciotti, Jessica^a | Porta, Natale^a | Iaiza, Alessia^c | Pastore, Antonio Luigi^d | Di Carlo, Angelina^e | Simone, Giuseppe^b | Carbone, Antonio^{d; 2} | Gallucci, Michele^{b; f; 2} | Fazi, Francesco^{c; 2; *}

Affiliations: [a] Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Pathology Unit ICOT, Latina, Italy | [b] Department of Urology, IRCCS – Regina Elena National Cancer Institute, Rome, Italy | [c] Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Section of Histology and Medical Embryology, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy | [d] Department of Medico Surgical Sciences and Biotechnologies, Sapienza University of Rome, Urology Unit ICOT, Latina, Italy | [e] Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy | [f] Department of Urology, Sapienza University of Rome, Rome, Italy

Correspondence: [*] Corresponding author: Francesco Fazi, Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Section of Histology and Medical Embryology, Sapienza University of Rome, Via A. Scarpa, 14-16, 00161 Rome, Italy. Tel.: +39 6 49766575; Fax: +39 6 4462854; E-mail: [email protected].

Note: [1] These authors have contributed equally to this work.

Note: [2] Co-last authors.

Abstract: BACKGROUND: MicroRNAs (miRNAs) are emerging as promising molecules in the diagnosis, prognosis and treatment of urological tumours. Recently, our group performed two independent studies highlighting that miR-210-3p may be a useful biomarker not only for diagnosis but also for post-surgery clear cell Renal Cell Carcinoma (ccRCC) management. OBJECTIVE: The aim of this study is to further explore the effectiveness of miRNA as non-invasive biomarker for clinical outcomes and ccRCC response to the treatment. METHODS: We analyzed miR-210-3p levels in neoplastic and healthy tissue and in urine specimens collected at surgery and during follow-up of 21 ccRCC patients by RTqPCR. RESULTS: Firstly, we confirmed that the expression of miR-210-3p was upregulated in tumor tissues and in urine samples of analyzed cohort. Of note is that miR-210-3p expression was significantly reduced in urine samples from disease-free patients during follow-up (from 3 to 12 months) compared to the baseline levels observed at the time of surgery. In a small subgroup of patients presenting metastatic progression (such as bone, intestinal or lung metastasis), the urine levels of miR-210-3p correlated with responsiveness to the therapy. CONCLUSIONS: This pilot study highlights the relevance of secreted miR-210-3p as powerful non-invasive prognostic and predictive biomarker for the evaluation of clinical outcomes and treatment response during ccRCC follow up.

Keywords: microRNA, miRNA, ccRCC, Cancer biomarkers, Liquid biopsy, metastasis, m miR-210

DOI: 10.3233/CBM-190242

Journal: Cancer Biomarkers, vol. 27, no. 2, pp. 181-188, 2020