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PLoS One
2015 Feb 23;102:e0117333. doi: 10.1371/journal.pone.0117333.
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Clinicopathological characteristics of patients with non-small-cell lung cancer who harbor EML4-ALK fusion gene: a meta-analysis.
Zhao F
,
Xu M
,
Lei H
,
Zhou Z
,
Wang L
,
Li P
,
Zhao J
,
Hu P
.
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).
CONCLUSION: 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.
Fig 2. Meta-analysis of data for EML4-ALK.(A smokers vs no-smokers; B adenocarcinomas vs non-adenocarcinomas; C stages I-II vs stages III-IV; D male vs female). Forest plot of the Relative Risk (RR) of the clinicopathological characteristics with EML4-ALK fusion gene patients. The RR estimate of each individual trial corresponds to the middle of the squares and the horizontal line gives the 95% CI. On each line, the numbers of events are represented as fractions of the total number; random choices are shown for both treatment groups. For each subgroup, the sum of the statistics, along with the summary RR are represented by the middle of the solid diamonds. A test of heterogeneity between the trials within a subgroup is given below in summary of the statistics.
Fig 3. Funnel plot of the outcome of clinicopathological characteristics and the EML4-ALK fusion gene.(smokers vs non-smokers; B adenocarcinomas vs non-adenocarcinomas; C stages I-II vs stages III-IV; D male vs female).
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