title: Circulating miR-182 is a biomarker of colorectal adenocarcinoma progression.
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.
authors.affiliation: Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; These authors contributed equally to this work.
authors.forename: Lisa
authors.initials: L
authors.lastname: Perilli
authors.affiliation: ARC-NET Research Centre, University of Verona, Verona, Italy; These authors contributed equally to this work.
authors.forename: Caterina
authors.initials: C
authors.lastname: Vicentini
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Surgery Section, University of Padua, Padua, Italy; Istituto di Ricerca Pediatrica - Citta' della Speranza, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Agostini
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pizzini
authors.affiliation: Department of Medicine , Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Pizzi
authors.affiliation: ARC-NET Research Centre, University of Verona, Verona, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: D'Angelo
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bortoluzzi
authors.affiliation: Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Istituto Oncologico Veneto (IOV), IRCCS, Padua, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Mandruzzato
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Surgery Section, University of Padua, Padua, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Mammano
authors.affiliation: Department of Medicine , Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, Surgery Section, University of Padua, Padua, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.affiliation: ARC-NET Research Centre, University of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: ARC-NET Research Centre, University of Verona, Verona, Italy; Department of Pathology and Diagnostics, University of Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Oncology and Immunology Section, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Istituto Oncologico Veneto (IOV), IRCCS, Padua, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Zanovello
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000235:genetics / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D015179:Colorectal Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D015513:Oncogene Proteins; C117634:ENTPD5 protein, human; D011755:Pyrophosphatases