Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression

// Lisa Perilli 1,* , Caterina Vicentini 3,* , Marco Agostini 4,5 , Silvia Pizzini 6 , Marco Pizzi 7 , Edoardo D’Angelo 3 , Stefania Bortoluzzi 6 , Susanna Mandruzzato 1,2 , Enzo Mammano 4 , Massimo Rugge 7 , Donato Nitti 4 , Aldo Scarpa 3,8 , Matteo Fassan 3,8 and Paola Zanovello 1,2 1 Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy 2 Istituto Oncologico Veneto (IOV), IRCCS, Padua, Italy 3 ARC-NET Research Centre, University of Verona, Verona, Italy 4 Department of Surgery, Oncology and Gastroenterology, Surgery Section University of Padua, Padua, Italy 5 Istituto di Ricerca Pediatrica - Citta’ della Speranza, Padua, Italy 6 Department of Biology, University of Padua, Padua, Italy 7 Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy 8 Department of Pathology and Diagnostics, University of Verona, Verona, Italy * These authors contributed equally to this work Correspondence: Matteo Fassan, email: // Keywords : miR-182, colon cancer, biomarkers, plasma Received : June 03, 2014 Accepted : July 22, 2014 Published : July 23, 2014 Abstract MiR-182 expression was evaluated by qRT-PCR and in situ hybridization in 20 tubular adenomas, 50 colorectal carcinoma (CRC), and 40 CRC liver metastases. Control samples obtained from patients with irritable bowel syndrome, or tumor-matched normal colon mucosa were analyzed (n=50). MiR-182 expression increased progressively and significantly along with the colorectal carcinogenesis cascade, and in CRC liver metastases. The inverse relation between miR-182 and the expression of its target gene ENTPD5 was investigated by immunohistochemical analysis. We observed that normal colocytes featured a strong ENTPD5 cytoplasmic expression whereas a significantly and progressively lower expression was present along with dedifferentiation of the histologic phenotype. Plasma samples from 51 CRC patients and controls were tested for miR-182 expression. Plasma miR-182 concentrations were significantly higher in CRC patients than in healthy controls or patients with colon polyps at endoscopy. Moreover, miR-182 plasma levels were significantly reduced in post-operative samples after radical hepatic metastasectomy compared to preoperative samples. Our results strengthen the hypothesis of a central role of miR-182 dysregulation in colon mucosa transformation, demonstrate the concomitant progressive down-regulation of ENTPD5 levels during colon carcinogenesis, and indicate the potential of circulating miR-182 as blood based biomarker for screening and monitoring CRC during the follow-up.