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Oncotarget. 2014 Aug 30;5(16):6611-9.

Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression.

Author information

1
Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; These authors contributed equally to this work.
2
ARC-NET Research Centre, University of Verona, Verona, Italy; These authors contributed equally to this work.
3
Department of Surgery, Oncology and Gastroenterology, Surgery Section, University of Padua, Padua, Italy; Istituto di Ricerca Pediatrica - Citta' della Speranza, Padua, Italy.
4
Department of Biology, University of Padua, Padua, Italy.
5
Department of Medicine , Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
6
ARC-NET Research Centre, University of Verona, Verona, Italy.
7
Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Istituto Oncologico Veneto (IOV), IRCCS, Padua, Italy.
8
Department of Surgery, Oncology and Gastroenterology, Surgery Section, University of Padua, Padua, Italy.
9
ARC-NET Research Centre, University of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy.

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.

PMID:
25115394
PMCID:
PMC4196150
DOI:
10.18632/oncotarget.2245
[Indexed for MEDLINE]
Free PMC Article

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