Association between serum uric acid levels and gastric cancer risk: a systematic review, integrated meta-analysis,...

Uric acid (UA) is the end product of purine metabolism. Numerous studies have reported an association between serum UA levels and the risk of several solid tumors, but its association with gastric cancer (GC) remains controversial. This study aims to explore the relationship between serum uric acid (SUA) and GC, to inform GC prevention and treatment strategies.

Literature searches were conducted in PubMed, Embase, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI). Mean differences (MD) with 95% confidence intervals (95% CI) were calculated using fixed or random effects models. Subgroup analysis was performed to explore heterogeneity sources. Additionally, bioinformatics analyses were carried out using publicly available datasets from the Gene Expression Omnibus (GEO), STRING, and DAVID databases to identify shared molecular pathways.

Six studies met the inclusion criteria. Meta-analysis revealed significantly higher SUA levels in GC patients compared to controls (pooled MD: 48.74; 95% CI 35.23-62.25; P < 0.00001; pooled SMD: 1.52, 95% CI 0.69-2.34), with extreme high heterogeneity was observed (I² = 89%, P < 0.00001; I² = 98%, P < 0.00001). Subgroup analysis based on control types presented numerical differences in pooled MD values between healthy control group (MD: 55.73; 95% CI 51.29-60.17; P = 0.33) and non-healthy control group (MD: 27.82; 95% CI - 7.87-63.51; P = 0.0006), while no statistically significant difference was detected in the healthy control subgroup. No publication bias was detected (P = 0.175). Bioinformatics analysis identified 188 overlapping differentially expressed genes (DEGs) between hyperuricemia and GC. Protein-protein interaction (PPI) network analysis highlighted IL6, TNF, and CXCL8 as central hub genes. Functional enrichment analysis showed enrichment trends in inflammatory pathways such as the IL-17 signaling axis, as well as interactions between viral proteins and cytokine receptors. These enrichment results provide preliminary bioinformatic clues that the correlation between SUA and GC may be associated with inflammatory response, immune microenvironment alteration and gastric mucosal barrier-related biological processes.

Our findings suggest a possible correlation between elevated SUA levels and GC, with a more obvious numerical trend in studies adopting healthy population controls. Elevated SUA may correlate with GC, especially in studies using healthy controls. Inflammation and immune dysregulation pathways likely underlie this association. SUA shows preliminary potential as a GC-related biomarker, though clinical use is unconfirmed. Large-sample prospective studies and basic experiments are needed to verify the correlation and mechanisms.