title: Digital PCR identifies changes in CDH1 (E-cadherin) transcription pattern in intestinal-type gastric cancer.
abstract: E-cadherin is a cell-cell adhesion protein encoded by CDH1 tumor-suppressor gene. CDH1 inactivating mutations, leading to loss of protein expression, are common in gastric cancer of the diffuse histotype, while alternative mechanisms modulating E-cadherin expression characterize the more common intestinal histotype. These mechanisms are still poorly understood. CDH1 intron 2 has recently emerged as a cis-modulator of E-cadherin expression, encoding non-canonical transcripts. One in particular, CDH1a, proved to be expressed in gastric cancer cell lines, while being absent in the normal stomach. For the first time, we evaluated by digital PCR the expression of CDH1 and CDH1a transcripts in cancer and normal tissue samples from 32 patients with intestinal-type gastric cancer. We found a significant decrease in CDH1 expression in tumors compared to normal counterparts (P = 0.001), which was especially evident in 76% of cases. CDH1a was detected at extremely low levels in 47% of tumors, but not in normal mucosa. A trend was observed of having less CDH1 in tumors expressing CDH1atranscript. The majority of tumors with both a decrease in CDH1 and presence of CDH1a also showed a decrease in miR-101 expression levels. On the whole, the decrease of CDH1 transcript, corresponding to the canonical protein, and the presence of CDH1a, corresponding to an alternative isoform, are likely to perturb E-cadherin-mediated signaling and cell-cell adhesion, thus contributing to intestinal-type gastric carcinogenesis.
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors.forename: Raefa
authors.initials: R
authors.lastname: Abou Khouzam
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Molinari
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Samanta
authors.initials: S
authors.lastname: Salvi
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Marabelli
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Molinaro
authors.affiliation: Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche, Pavia, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Orioli
authors.affiliation: Pathology Unit, Morgagni-Pierantoni Hospital, Forlì, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Saragoni
authors.affiliation: Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Morgagni
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Calistri
authors.affiliation: Department of Biology and Biotechnology, University of Pavia, Pavia, Italy.
authors.forename: Guglielmina Nadia
authors.initials: GN
authors.lastname: Ranzani
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D059467:Transcriptome; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D020033:Protein Isoforms; D051176:beta Catenin
keywords: CDH1 transcripts; digital-PCR quantification; intestinal-type gastric cancer; normal gastric mucosa