Abstract
Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide. CXCL12, a chemokine involved in tumor progression and metastasis, has been inconsistently associated with GC survival. This meta-analysis aimed to evaluate the prognostic significance of CXCL12 expression in GC patients. A comprehensive literature search was conducted in PubMed, Embase, and Web of Science. Observational studies assessing tumor CXCL12 expression and survival outcomes in GC patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model by incorporating heterogeneity. Ten studies comprising 1361 GC patients were included. High CXCL12 expression was significantly associated with poorer overall survival (OS) (HR: 1.85, 95% CI 1.51-2.26, p < 0.001) with mild heterogeneity (I(2) = 17%). Subgroup analyses revealed that the association between high CXCL12 expression and OS was stronger in studies defining high expression as above the median density value (HR: 2.63, 95% CI 1.79-3.86) than in those using any positive expression (HR: 1.61, 95% CI 1.30-2.00; p for subgroup difference = 0.03). Additionally, a more pronounced association was observed in studies with follow-up durations ≥ 36 months (HR: 2.42, 95% CI 1.84-3.18) compared to those with < 36 months (HR: 1.59, 95% CI 1.28-1.99; p = 0.03). The pooled results also indicated an association between high CXCL12 expression and worse progression-free survival (PFS) (HR: 1.52, 95% CI 1.05-2.20, p = 0.03). High CXCL12 expression is associated with poorer survival outcomes in GC patients.