title: Clinicopathological characteristics of patients with non-small-cell lung cancer who harbor EML4-ALK fusion gene: a meta-analysis.
abstract: BACKGROUND
  A novel fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has been recently identified in non-small-cell lung cancers (NSCLCs). Patients with the EML4-ALK fusion gene demonstrate unique clinicopathological and physiological characteristics. Here we present a meta-analysis of large-scale studies to evaluate the clinicopathological characteristics of NSCLC patients harboring the EML4-ALK fusion gene.
  
  
  METHODS
  Both English and Chinese databases were systematically used to search the materials of the clinicopathological characteristics of patients with NSCLC harboring the EML4-ALK fusion gene. Pooled relative risk (RR) estimates and the 95% confidence intervals (95% CI) were calculated with the fixed or random effect model. Publication bias and chi-square test were also calculated.
  
  
  RESULTS
  27 retrospective studies were included in our meta-analysis. These studies included a total of 6950 patients. The incidence rate of EML4-ALK fusion in NSCLC patients was found to be 6.8% (472/6950). The correlation of the EML4-ALK fusion gene and clinicopathological characteristics of NSCLC patients demonstrated a significant difference in smoking status, histological types, stage, and ethnic characteristics. The positive rate of the EML4-ALK fusion gene expression in females were slightly higher than that in males, but not significantly (P = 0.52). In addition, the EML4-ALK fusion gene was mutually exclusive of the EGFR and KRAS mutation genes (P = 0.00).
  
  
  CONCLUSIONS
  Our pooled analysis revealed that the EML4-ALK fusion gene was observed predominantly in adenocarcinoma, non-smoking and NSCLC patients, especially those diagnosed in the advanced clinical stage of NSCLC. Additionally, the EML4-ALK fusion gene was exclusive of the EGFR and KRAS mutation genes. We surmise that IHC assay is a valuable tool for the prescreening of patients with ALK fusion gene in clinical practice, and FISH assay can be performed as a confirmation method. These insights might be helpful in guiding the appropriate molecular target therapy for NSCLC.
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Fengzhi
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Honcho
authors.initials: H
authors.lastname: Lei
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Ziqi
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Jianfu
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Oncology, the First Affiliated Hospital, Jinan University, Guangzhou, China.
authors.forename: Penghui
authors.initials: P
authors.lastname: Hu
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000503:physiopathology*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics
chemical_list: C522504:EML4-ALK fusion protein, human; C117307:KRAS protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins