Clinicopathological Characteristics of Patients with Non-Small-Cell Lung Cancer Who Harbor <i>EML4-ALK</i> Fusion Gene: A Meta-Analysis

<div><p>Background</p><p>A novel fusion gene of echinoderm microtubule-associated protein-like 4 (<i>EML4</i>) and anaplastic lymphoma kinase (<i>ALK</i>) has been recently identified in non-small-cell lung cancers (NSCLCs). Patients with the <i>EML4-ALK</i> 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 <i>EML4-ALK</i> fusion gene.</p><p>Methods</p><p>Both English and Chinese databases were systematically used to search the materials of the clinicopathological characteristics of patients with NSCLC harboring the <i>EML4-ALK</i> 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.</p><p>Results</p><p>27 retrospective studies were included in our meta-analysis. These studies included a total of 6950 patients. The incidence rate of <i>EML4-ALK</i> fusion in NSCLC patients was found to be 6.8% (472/6950). The correlation of the <i>EML4-ALK</i> 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 <i>EML4-ALK</i> fusion gene expression in females were slightly higher than that in males, but not significantly (<i>P</i> = 0.52). In addition, the <i>EML4-ALK</i> fusion gene was mutually exclusive of the <i>EGFR</i> and <i>KRAS</i> mutation genes (<i>P</i> = 0.00).</p><p>Conclusion</p><p>Our pooled analysis revealed that the <i>EML4-ALK</i> fusion gene was observed predominantly in adenocarcinoma, non-smoking and NSCLC patients, especially those diagnosed in the advanced clinical stage of NSCLC. Additionally, the <i>EML4-ALK</i> fusion gene was exclusive of the <i>EGFR</i> and <i>KRAS</i> mutation genes. We surmise that IHC assay is a valuable tool for the prescreening of patients with <i>ALK</i> 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.</p>