Let-7c down-regulation in Helicobacter pylori-related gastric carcinogenesis
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Matteo Fassan1, Deborah Saraggi1, Laura Balsamo1, Luciano Cascione2, Carlo Castoro3, Irene Coati1, Marina De Bernard4, Fabio Farinati5, Vincenza Guzzardo1, Nicola Valeri6, Carlo Federico Zambon7, Massimo Rugge1
1Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy
2Institute of Oncology Research and Swiss Institute of Bioinformatics, Lymphoma & Genomics Group, Bellinzona, Switzerland
3Istituto Oncologico Veneto, IOV-IRCCS, Surgery Unit, Padua, Italy
4Department of Biology, University of Padua, Padua, Italy
5Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy
6Molecular Pathology Division, Institute of Cancer Research, London and Sutton, UK
7Department of Medicine (DIMED), Clinical Pathology Unit, University of Padua, Padua, Italy
Massimo Rugge, e-mail: email@example.com
Keywords: microRNA, gastric adenocarcinoma, Helicobacter pylori, preneoplastic lesions
Received: September 18, 2015 Accepted: November 27, 2015 Published: December 17, 2015
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.
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