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Let-7c down-regulation in Helicobacter pylori -related gastric carcinogenesis

2015; Impact Journals LLC; Volume: 7; Issue: 4 Linguagem: Inglês

10.18632/oncotarget.6642

1949-2553

Matteo Fassan, Deborah Saraggi, Laura Balsamo, Luciano Cascione, Carlo Castoro, Irene Coati, Marina de Bernard, Fabio Farinati, Vincenza Guzzardo, Nicola Valeri, Carlo–Federico Zambon, Massimo Rugge,

Gastric Cancer Management and Outcomes

// Matteo Fassan 1 , Deborah Saraggi 1 , Laura Balsamo 1 , Luciano Cascione 2 , Carlo Castoro 3 , Irene Coati 1 , Marina De Bernard 4 , Fabio Farinati 5 , Vincenza Guzzardo 1 , Nicola Valeri 6 , Carlo Federico Zambon 7 , Massimo Rugge 1 1 Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy 2 Institute of Oncology Research and Swiss Institute of Bioinformatics, Lymphoma & Genomics Group, Bellinzona, Switzerland 3 Istituto Oncologico Veneto, IOV-IRCCS, Surgery Unit, Padua, Italy 4 Department of Biology, University of Padua, Padua, Italy 5 Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy 6 Molecular Pathology Division, Institute of Cancer Research, London and Sutton, UK 7 Department of Medicine (DIMED), Clinical Pathology Unit, University of Padua, Padua, Italy Correspondence to: Massimo Rugge, e-mail: massimo.rugge@unipd.it Keywords: microRNA, gastric adenocarcinoma, Helicobacter pylori, preneoplastic lesions Received: September 18, 2015 Accepted: November 27, 2015 Published: December 17, 2015 ABSTRACT Aberrant let-7c microRNA (miRNA) expression has been observed in Helicobacter pylori -related gastric cancer (GC) but fragmentary information is available on the let-7c dysregulation occurring with each phenotypic change involved in gastric carcinogenesis. Let-7c expression was assessed (qRT-PCR) in a series of 175 gastric biopsy samples representative of the whole spectrum of phenotypic changes involved in H. pylori -related gastric oncogenesis including: i) normal gastric mucosa, as obtained from dyspeptic controls (40 biopsy samples); ii) non-atrophic gastritis (40 samples); iii) atrophic-metaplastic gastritis (35 samples); iv) intra-epithelial neoplasia (30 samples); v) GC (30 samples). Let-7c expression was also tested in 20 biopsy samples obtained from 10 patients before and after H. pylori eradication therapy (median follow-up: 10 weeks; range: 7-14). The results obtained were further validated by in situ hybridization on multiple tissue specimens obtained from 5 surgically treated H. pylori -related GCs. The study also included 40 oxyntic biopsy samples obtained from serologically/histologically confirmed autoimmune gastritis (AIG: 20 corpus-restricted, non-atrophic; 20 corpus-restricted, atrophic-metaplastic). Let-7c expression dropped from non-atrophic gastritis to atrophic-metaplastic gastritis, intra-epithelial neoplasia, and invasive GC ( p <0.001). It rose again significantly following H. pylori eradication ( p =0.009). As in the H. pylori model, AIG also featured a significant let-7c down-regulation ( p <0.001). The earliest phases of the two pathways to gastric oncogenesis ( H. pylori -environmental and autoimmune host-related) are characterized by similar let-7c dysregulations. In H. pylori infection, let-7c down-regulation regresses after the bacterium's eradication, while it progresses significantly with the increasing severity of the histological lesions.