Oncotarget

Clinical Research Papers:

Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression

Lisa Perilli, Caterina Vicentini, Marco Agostini, Silvia Pizzini, Marco Pizzi, Edoardo D’ D. Angelo, Stefania Bortoluzzi, Susanna Mandruzzato, Enzo Mammano, Massimo Rugge, Donato Nitti, Aldo Scarpa, Matteo Fassan _ and Paola Zanovello

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Oncotarget. 2014; 5:6611-6619. https://doi.org/10.18632/oncotarget.2245

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Abstract

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

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.


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