Background: The C-X-C Motif Chemokine Receptor (CXCR4) is an oncogene that has been widely studied and associated with worse clinicopathological features and prognosis outcomes in many types of cancer. Besides that, significance of CXCR4 expression on clinicopathological features and prognostic factors in osteosarcoma (OS) requires further validation.

Aim: We conducted a meta-analysis to evaluate the association between positive CXCR4 expression with clinicopathological features and prognosis in OS.

Methods: Literature searches on Pubmed, Cochrane Library, and Web of Science were conducted systematically up to December 2021 to find relevant references. The effects of CXCR4 expression on clinicopathological characteristics and prognostic were analyzed using Review Manager 5.4 (Cochrane Collaboration, Oxford, UK). A significance value less than 0.05 was considered statistically significant.

Results: By considering inclusion and exclusion criteria, 940 patients from 12 studies were suitable for qualitative analysis, and 10 studies were suitable for quantitative analysis. Association between CXCR4 expression and OS clinicopathological features was found significant on metastasis (OR= 4.01, 95%CI= 1.58-10.18; p= 0.003), stage (stage III & IV vs I & II, OR= 6.52, 95%CI= 1.05-40.62; p= 0.04), and tumor primary site (femur/tibia vs other, OR= 1.60, 95%CI= 1.04-2.45; p= 0.03), but not associated with histological type, gender, and age. Furthermore, CXCR4 expression is associated with poor overall survival in OS (HR= 2.13, 95%CI= 1.78-2.55; p <0.001).

Conclusion: In conclusion, the results of our meta-analysis suggest that CXCR4 expression may be valuable as a histopathological predictor of poor clinicopathological features and prognosis of OS.

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