title: The relationship between EGFR gain and VHL loss in lung adenocarcinoma and poor patient survival.
abstract: BACKGROUND
  The prognosis of lung cancer remains poor and clinically applicable prognostic markers have not yet been satisfactory identified. Several chromosomal copy number alterations (CNAs) have been associated with metastasis, relapse, and survival of patients with lung cancer; however, no study has focused exclusively on identifying CNAs at a gene level. The aim of this study was to identify genes whose CNAs are associated with survival of patients with lung adenocarcinoma.
  
  
  METHODS
  The CNA status of a panel of 48 genes was detected by high-resolution array comparative genomic hybridization in 56 lung adenocarcinoma samples. The follow-up time of these patients was 8.5-65.7 months. The gene CNAs were analyzed for their association with patient survival.
  
  
  RESULTS
  Cox univariate regression analysis revealed that EGFR gain (hazard ratio (HR) 3.84, 95% confidence interval (CI) 1.62-9.10), VHL loss (HR 4.56, 95% CI 1.85-11.27) and WWOX loss (HR 4.14, 95% CI 1.60-10.69) were each associated with poor survival. Multivariate analyses including EGFR gain, VHL loss and WWOX loss, as well as the clinicopathological variables such as age, sex, tumor size, tumor differentiation and TNM stage showed that EGFR gain (HR 4.63, 95% CI 1.69-12.7) and VHL loss (HR 4.82, 95% CI 1.41-16.43) were independent prognostic factors for poor survival, whereas WWOX loss lost statistical significance.
  
  
  CONCLUSIONS
  These findings suggest that EGFR gain and VHL loss are associated with poor overall survival for lung adenocarcinoma patients and may be used as prognostic markers.
authors.affiliation: Department of Cardiovascular Surgery, The Fourth Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.forename: Shengfa
authors.initials: S
authors.lastname: Wang
authors.forename: Hongguang
authors.initials: H
authors.lastname: Lu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Chen
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yubin
authors.initials: Y
authors.lastname: Jin
authors.forename: Zhong-Zheng
authors.initials: ZZ
authors.lastname: Zhu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D055028:Comparative Genomic Hybridization; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage; D056726:Genetic Association Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010088:Oxidoreductases / Q000235:genetics; D011379:Prognosis; D013223:Statistics as Topic; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C512478:EGFR protein, human; D066246:ErbB Receptors; C497446:VHL protein, human