title: Claudin-4 expression predicts survival in pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  Identification of prognostic markers would be useful in the clinical management of patients with pancreatic ductal adenocarcinoma (PDAC). The clinical relevance of claudin-4 (CLDN4), recently identified as overexpressed in PDAC, is unknown.
  
  
  METHODS
  Using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR), we analyzed CLDN4 mRNA expression in a panel of 9 pancreatic cancer cell lines and formalin-fixed paraffin-embedded (FFPE) tissues from 100 patients with PDAC. The CLDN4 expression levels were then correlated with clinicopathological variables and patient outcome. We also performed immunohistochemical analysis in 20 FFPE samples of PDAC to investigate the expression of CLDN4 protein.
  
  
  RESULTS
  Increased expression of CLDN4 was confirmed in all the pancreatic cancer cell lines tested compared with normal ductal epithelial cells and fibroblasts. We found that low expression of CLDN4 was significantly associated with shorter survival in patients with PDAC (hazard ratio; 1.362, 95% confidence interval; 1.011-1.873, P = 0.0419). Patients with high CLDN4 expression survived longer for a median of 63.0 months, compared with 14.7 months in patients with low CLDN4 expression (P = 0.0067). In immunohistochemical analysis, the level of CLDN4 mRNA expression was significantly correlated with the expression of CLDN4 protein (P = 0.0168).
  
  
  CONCLUSIONS
  Increased expression of CLDN4 mRNA predicts better prognosis in PDAC.
authors.affiliation: Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.forename: Reiko
authors.initials: R
authors.lastname: Tanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Katsuya
authors.initials: K
authors.lastname: Morimatsu
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kayashima
authors.forename: Hayato
authors.initials: H
authors.lastname: Fujita
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takahata
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D062506:Claudin-4 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D010180:Pancreatectomy; D010183:Pancreatic Ducts; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D014408:Biomarkers, Tumor; C568157:CLDN4 protein, human; D062506:Claudin-4; D012333:RNA, Messenger