title: Aberrant expression of EphA3 in gastric carcinoma: correlation with tumor angiogenesis and survival.
abstract: BACKGROUND
  EphA3, a member of the Eph receptor tyrosine kinases, plays important roles in tumor angiogenesis and progression. However, the function of EphA3 in solid tumors has not been widely studied. We aimed to explore EphA3 expression in gastric carcinoma and analyze its role as a potential prognostic factor.
  
  
  METHODS
  Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to assess EphA3 mRNA in a normal gastric mucosa cell line and carcinoma cell lines. Immunohistochemistry for EphA3 and vascular endothelial growth factor (VEGF) was performed in 318 cases of gastric carcinoma. CD34 immunohistochemical staining was used for microvessel density (MVD) counting. Western blotting was used to analyze EphA3 expression in the cell lines and to determine the expression of EphA3 and VEGF in 75 cases of gastric carcinoma and matched normal mucosa.
  
  
  RESULTS
  EphA3 mRNA and protein expression was significantly higher in gastric cancer than that in normal mucosa (all P < 0.001). EphA3 was significantly correlated with TNM stage and poor prognosis (all P < 0.001). Multivariate analysis showed that EphA3 had an independent effect on survival (P = 0.037). EphA3 was positively correlated with VEGF (P < 0.001), and MVD (P < 0.001). According to Western blot analysis, both EphA3 and VEGF expression were significantly higher in carcinoma than that in normal mucosa (all P < 0.001). A positive correlation was observed between EphA3 and VEGF expression in cancer (P < 0.001, r = 0.513).
  
  
  CONCLUSIONS
  EphA3 may play important roles in the angiogenesis and prognosis of gastric carcinoma, and thus may become a useful target for therapeutic intervention and a potential indicator for clinical assessment of tumor prognosis.
authors.affiliation: Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Hong-Qing
authors.initials: HQ
authors.lastname: Xi
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D036121:Receptor, EphA3; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C491718:EPHA3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3