title: Decreased expression of DAB2IP in pancreatic cancer with wild-type KRAS.
abstract: BACKGROUND
  KRAS mutation plays an important role in the pathogenesis of pancreatic cancer. However, the role of wild-type KRAS in the progression of pancreatic cancer remains unknown. The present study was to investigate the expression of the Ras GTPase activating protein (DAB2IP) in pancreatic cancer and its clinical significance.
  
  
  METHODS
  The expression of DAB2IP in pancreatic cancer cell lines and normal human pancreatic ductal epithelial cells was analyzed by Western blotting and real-time quantitative reverse transcription-PCR (qRT-PCR). The KRAS mutational types of pancreatic cancer tissues obtained from pancreatic cancer patients (n=20) were also analyzed. Subsequently, DAB2IP expression was detected in pancreatic cancer tissues, adjacent and normal pancreatic tissues (n=2) by immunohistochemistry, and the relationship between DAB2IP expression and the clinical characteristics of patients was evaluated.
  
  
  RESULTS
  Western blotting and qRT-PCR results showed that DAB2IP expression in pancreatic cancer cells with wild-type KRAS was lower than that in those with mutation-type KRAS and normal human pancreatic ductal epithelial cells (P<0.05). Immunohistochemistry showed that DAB2IP expression was lower in pancreatic cancer tissues than that in adjacent and normal pancreatic tissues (Z=-4.000, P=0.000). DAB2IP expression was lower in pancreatic cancer patients with the wild-type KRAS gene than that in those with KRAS mutations (WilcoxonW=35.000, P=0.042). Furthermore, DAB2IP expression in patients with perineurial invasion was lower than that in those without invasion (WilcoxonW=71.500, P=0.028). DAB2IP expression was lower in patients with more advanced stage than that in those with early clinical stage (WilcoxonW=54.000, P=0.002).
  
  
  CONCLUSIONS
  DAB2IP expression was reduced in patients with pancreatic cancer compared with those with no cancer. DAB2IP expression was correlated with the KRAS gene, perineurial invasion and clinical stage of the disease. Our data indicated that DAP2IP expression can be used as a potential prognostic indicator and a promising molecular target for therapeutic intervention in patients with pancreatic cancer.
authors.affiliation: Southern Medical University, Guangzhou 510515, China.
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Duan
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Li
authors.forename: Yan-Hui
authors.initials: YH
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Mei
authors.forename: Yu-Xuan
authors.initials: YX
authors.lastname: Qin
authors.forename: Liang-Fang
authors.initials: LF
authors.lastname: Li
authors.forename: Qiu-Xiong
authors.initials: QX
authors.lastname: Lin
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C462952:DAB2IP protein, human; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D020703:ras GTPase-Activating Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins