Abstract
BackgroundThe frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene.MethodsThe Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted.ResultsSeventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30–0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66–3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41–0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03–0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger's test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status.ConclusionThis meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR.
Highlights
Since the early 2000s, a more thorough understanding of the molecular biology of non-small cell lung cancer (NSCLC) has led to major advances in treatment of this neoplasm
Identification of mutations in the epidermal growth factor receptor (EGFR), K-ras gene, and most recently the echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (EML4-ALK) fusion gene have had a decisive impact on the treatment of NSCLC
Overall, when all the eligible studies were pooled into the meta-analysis (Fig. 2), no significant heterogeneity was observed (I2 = 37%, P = 0.07), we chose the fixed-effects model and found that a significantly lower EML4-ALK fusion gene positivity rate was associated with smokers
Summary
Since the early 2000s, a more thorough understanding of the molecular biology of non-small cell lung cancer (NSCLC) has led to major advances in treatment of this neoplasm. (involving 2p21 and 2p23; approximately 12 Mb apart) results in the formation of this fusion gene, which leads to constitutive ALK kinase activation, possessing potent oncogenic activity both in vitro and in vivo [2,3,4]. In these tumors, the EML4-ALK fusion gene is the determinant of critical growth pathways, resulting in the activation of PI3K/AKT and MAPK/ERK pathways downstream [1]. The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene
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