title: Let-7c down-regulation in Helicobacter pylori-related gastric carcinogenesis.
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.
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Saraggi
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Balsamo
authors.affiliation: Institute of Oncology Research and Swiss Institute of Bioinformatics, Lymphoma & Genomics Group, Bellinzona, Switzerland.
authors.forename: Luciano
authors.initials: L
authors.lastname: Cascione
authors.affiliation: Istituto Oncologico Veneto, IOV-IRCCS, Surgery Unit, Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castoro
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Coati
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: De Bernard
authors.affiliation: Department of Surgical Oncology and Gastroenterology (DiSCOG), Gastroenterology Unit, University of Padua, Padua, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.affiliation: Molecular Pathology Division, Institute of Cancer Research, London and Sutton, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Valeri
authors.affiliation: Department of Medicine (DIMED), Clinical Pathology Unit, University of Padua, Padua, Italy.
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Zambon
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D063646:Carcinogenesis; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human
keywords: Helicobacter pylori; gastric adenocarcinoma; microRNA; preneoplastic lesions