title: KIAA1199/CEMIP/HYBID overexpression predicts poor prognosis in pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  KIAA1199 (also known as CEMIP or HYBID), a newly identified protein involved in hyaluronan degradation, has been suggested to play a critical role in cancer progression. The aim of this study was to investigate the expression and functional significance of KIAA1199 in pancreatic ductal adenocarcinoma (PDAC).
  
  
  METHODS
  Using quantitative real-time RT-PCR, we analyzed KIAA1199 mRNA expression in 6 PDAC cell lines and frozen tissues from 14 patients with PDAC. We also used immunohistochemistry to analyze KIAA1199 protein expression in formalin-fixed, paraffin-embedded tissues from 98 patients with PDAC. The KIAA1199 expression pattern was then correlated with clinicopathological variables and patient outcome. The effect of KIAA1199 on migratory ability of PDAC cells was determined by KIAA1199 knockdown with small-interfering RNA (siRNA).
  
  
  RESULTS
  The KIAA1199 mRNA expression was significantly higher in PDAC tissues than in the corresponding non-tumor tissues (P < 0.0001). Immunohistochemical analysis revealed high expression of KIAA1199 in 26 (26.5%) of 98 PDAC tissues. The overall survival was significantly shorter in patients with high KIAA1199 expression than in patients with low KIAA1199 expression (P = 0.0001). In multivariate analysis, high KIAA1199 expression (P = 0.003) and UICC stage (P = 0.003) were independent factors predicting poor prognosis. Furthermore, the KIAA1199 mRNA expression was higher in most PDAC cell lines and siRNA knockdown of KIAA1199 resulted in decreased migration.
  
  
  CONCLUSIONS
  These findings suggest that overexpression of KIAA1199 may contribute to increased migration of PDAC cells and predict shorter survival after surgical resection.
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Koga
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan. Electronic address: norisato@med.uoeh-u.ac.jp.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Kohi
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan; Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yabuki
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Cheng
authors.affiliation: Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hisaoka
authors.affiliation: Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006821:Hyaluronoglucosaminidase; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D011506:Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins; C491433:CEMIP protein, human; D006821:Hyaluronoglucosaminidase
keywords: Hyaluronan; KIAA1199; Migration; Pancreatic ductal adenocarcinoma; Prognosis