A meta-analysis for C-X-C chemokine receptor type 4 as a prognostic marker and potential drug target in hepatocellular carcinoma

Fei Hu, Lin Miao, Yu Zhao, Yuan-Yuan Xiao, Qing Xu

Department of Medical Oncology, Shanghai Tenth People’s Hospital, Tongji University, School of Medicine, Shanghai, People’s Republic of China

Abstract: Chemokines (CKs), small proinflammatory chemoattractant cytokines that bind to specific G-protein coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. C-X-C chemokine receptor type 4 (CXCR4) has gained tremendous attention over the last decade, since it was found to be upregulated in a wide variety of cancer types, including hepatocellular carcinoma (HCC). The clinical relevance of expression of CXCR4 in HCC remains controversial; our aim was to identify the precise relationship of CXCR4 to prognosis and clinicopathological features. We searched the database from MEDLINE, PubMed, Web of Science, Scopus and Embase and then conducted a meta-analysis from publications met the inclusion criteria for the qualitative study. Our data showed that 1) CXCR4 is overexpressed in HCC tissues but not in normal hepatic tissue, OR =84.26, 95% confidence interval (CI) =11.86–598.98, P<0.0001. CXCR4 expression is higher in HCC than those in cirrhosis as well, OR =20.71, 95% CI =7.61–56.34, P<0.00001. 2) The expression levels of CXCR4 does not increase during local progression, however, CXCR4 expression increases the risk of distant metastases in HCC, OR =5.84, 95% CI =2.84–12.00, P<0.00001. 3) High levels of CXCR4 gene expression are associated with worse survival in HCC, HR =0.18, 95% CI =0.10–0.32, Z=5.77, P<0.00001. These data indicate that CXCR4 expression correlates with an increased risk and worse survival in HCC patients. The aberrant CXCR4 expression plays an important role in the carcinogenesis and metastasis of HCC. Our conclusion also supports that the promise of CXCR4 signaling pathway blockade as a potential strategy for HCC patients.

Keywords: CXCR4, CXCL12, prognosis, marker, hepatocellular carcinoma, cirrhosis, meta-analysis