Clinical Research Papers:
Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression
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Lisa Perilli1,*, Caterina Vicentini3,*, Marco Agostini4,5, Silvia Pizzini6, Marco Pizzi7, Edoardo D’Angelo3, Stefania Bortoluzzi6, Susanna Mandruzzato1,2, Enzo Mammano4, Massimo Rugge7, Donato Nitti4, Aldo Scarpa3,8, Matteo Fassan3,8 and Paola Zanovello1,2
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
Matteo Fassan, email:
Keywords: miR-182, colon cancer, biomarkers, plasma
Received: June 03, 2014 Accepted: July 22, 2014 Published: July 23, 2014
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.
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