title: MET gene copy number predicts worse overall survival in patients with non-small cell lung cancer (NSCLC); a systematic review and meta-analysis.
abstract: OBJECTIVE
  MET is a receptor present in the membrane of NSCLC cells and is known to promote cell proliferation, survival and migration. MET gene copy number is a common genetic alteration and inhibition o MET emerges as a promising targeted therapy in NSCLC. Here we aim to combine in a meta-analysis, data on the effect of high MET gene copy number on the overall survival of patients with resected NSCLC.
  
  
  METHODS
  Two independent investigators applied parallel search strategies with the terms "MET AND lung cancer", "MET AND NSCLC", "MET gene copy number AND prognosis" in PubMed through January 2014. We selected the studies that investigated the association of MET gene copy number with survival, in patients who received surgery.
  
  
  RESULTS
  Among 1096 titles that were identified in the initial search, we retrieved 9 studies on retrospective cohorts with adequate retrievable data regarding the prognostic impact of MET gene copy number on the survival of patients with NSCLC. Out of those, 6 used FISH and the remaining 3 used RT PCR to assess the MET gene copy number in the primary tumor. We calculated the I2 statistic to assess heterogeneity (I2 = 72%). MET gene copy number predicted worse overall survival when all studies were combined in a random effects model (HR = 1.78, 95% CI 1.22-2.60). When only the studies that had at least 50% of adenocarcinoma patients in their populations were included, the effect was significant (five studies, HR 1.55, 95% CI 1.23-1.94). This was not true when we included only the studies with no more than 50% of the patients having adenocarcinoma histology (four studies HR 2.18, 95% CI 0.97-4.90).
  
  
  CONCLUSIONS
  Higher MET gene copy number in the primary tumor at the time of diagnosis predicts worse outcome in patients with NSCLC. This prognostic impact may be adenocarcinoma histology specific.
authors.affiliation: Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Dimou
authors.affiliation: Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Lemuel
authors.initials: L
authors.lastname: Non
authors.affiliation: Northwestern Medicine Developmental Therapeutics Institute (NMDTI), Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, United States of America.
authors.forename: Young Kwang
authors.initials: YK
authors.lastname: Chae
authors.affiliation: Albert Einstein Healthcare Network, Cancer Center, Albert Einstein Medical Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Tester
authors.affiliation: Sotiria General Hospital Cancer Center, The University of Athens, Athens, Greece.
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Syrigos
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality*; D066246:ErbB Receptors / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D011518:Proto-Oncogene Proteins; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; C491743:MET protein, human; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases