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C-X-C chemokine receptor 4 (CXCR4) is frequently over-expressed in various types of cancer; many agents against CXCR4 are in clinical development currently despite variable data for the prognostic impact of CXCR4 expression. Here eighty-five studies with a total of 11,032 subjects were included to explore the association between CXCR4 and progression-free survival (PFS) or overall survival (OS) in subjects with cancer. Pooled analysis shows that CXCR4 over-expression is significantly associated with poorer PFS (HR 2.04; 95% CI, 1.72-2.42) and OS (HR=1.94; 95% CI, 1.71-2.20) irrespective of cancer types. Subgroup analysis indicates significant association between CXCR4 and shorter PFS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, renal cancer, gynecologic cancer, pancreatic cancer and liver cancer; the prognostic effects remained consistent across age, risk of bias, levels of adjustment, median follow-up period, geographical area, detection methods, publication year and size of studies. CXCR4 over-expression predicts unfavorable OS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, head and neck cancer, renal cancer, lung cancer, gynecologic cancer, liver cancer, prostate cancer and gallbladder cancer; these effects were independence of age, levels of adjustment, publication year, detection methods and follow-up period. In conclusion, CXCR4 over-expression is associated with poor prognosis in cancer.

CXCR4 over-expression and survival in cancer: A system review and meta-analysis