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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4915-4924
Number of pages10
JournalOncotarget
Volume7
Issue number4
DOIs
Publication statusPublished - 2016

Keywords

  • Gastric adenocarcinoma
  • Helicobacter pylori
  • MicroRNA
  • Preneoplastic lesions

ASJC Scopus subject areas

  • Oncology

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