title: Identification of novel transmembrane proteins in scirrhous-type gastric cancer by the Escherichia coli ampicillin secretion trap (CAST) method: TM9SF3 participates in tumor invasion and serves as a prognostic factor.
abstract: OBJECTIVE
  Scirrhous-type gastric cancer (GC) is highly aggressive and has a poor prognosis due to rapid cancer cell infiltration accompanied by extensive stromal fibrosis. The aim of this study is to identify genes that encode transmembrane proteins frequently expressed in scirrhous-type GC.
  
  
  METHODS
  We compared Escherichia coli ampicillin secretion trap (CAST) libraries from 2 human scirrhous-type GC tissues with a normal stomach CAST library. By sequencing 2,880 colonies from scirrhous CAST libraries, we identified a list of candidate genes.
  
  
  RESULTS
  We focused on the TM9SF3 gene because it has the highest clone count, and immunohistochemical analysis demonstrated that 46 (50%) of 91 GC cases were positive for TM9SF3, which was observed frequently in scirrhous-type GC. TM9SF3 expression showed a significant correlation with the depth of invasion, tumor stage and undifferentiated GC. There was a strong correlation between TM9SF3 expression and poor patient outcome, which was validated in two separate cohorts by immunostaining and quantitative RT-PCR, respectively. Transient knockdown of the TM9SF3 gene by siRNA showed decreased tumor cell-invasive capacity.
  
  
  CONCLUSIONS
  Our results indicate that TM9SF3 might be a potential diagnostic and therapeutic target for scirrhous-type GC.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Htoo Zarni
authors.initials: HZ
authors.lastname: Oo
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Anami
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Naito
authors.forename: Takashi
authors.initials: T
authors.lastname: Oshima
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D002293:Adenocarcinoma, Scirrhous / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*; D000368:Aged; D000667:Ampicillin; D014408:Biomarkers, Tumor / Q000235:genetics / Q000502:physiology; D002352:Carrier Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D004926:Escherichia coli; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000503:physiopathology; D011379:Prognosis; D021382:Protein Sorting Signals; D034741:RNA, Small Interfering / Q000494:pharmacology; D017422:Sequence Analysis, DNA / Q000379:methods*; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D034741:RNA, Small Interfering; C437715:TM9SF3 protein, human; D000667:Ampicillin