A meta-analysis for CXCR4 as a prognostic marker and potential drug target in non-small cell lung cancer

BACKGROUND Recent reports have shown that C-X-C chemokine receptor type 4 (CXCR4) is a candidate oncogene in several types of human tumors, including non-small cell lung cancer (NSCLC). However, the correlation between CXCR4 expression and clinicopathological characteristics of NSCLC remains controversial and has not been emphasized. The aim of this study is to quantitatively evaluate the association of CXCR4 expression with the incidence of NSCLC and clinicopathological characteristics by performing a meta-analysis. METHODS A detailed literature search was carried out for related research publications. Only articles in which CXCR4 expression was detected by immunohistochemical staining were included. Odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were calculated and summarized. RESULTS Final analysis of 1,872 NSCLC patients from 19 eligible studies was performed. We observed that CXCR4 expression was significantly higher in NSCLC than in normal lung tissue, based on the pooled OR from ten studies, including 678 NSCLCs and 189 normal lung tissues (OR =16.66, 95% CI =6.94-40.02, P<0.00001). CXCR4 expression was also significantly associated with clinical stages, metastatic status, and overall survival (OS) in NSCLC patients. In addition, CXCR4 mRNA high expression was found to correlate with worse OS of all NSCLC patients followed for 20 years, HR =1.24, P=0.0047. CONCLUSION The present meta-analysis indicated that CXCR4 protein expression is associated with an increased risk and worse survival in NSCLC patients. The aberrant CXCR4 protein and mRNA expression play an important role in the carcinogenesis and metastasis of NSCLC.