Abstract
BACKGROUND: Inflammation significantly affects the progression of gastric cancer (GC). The Systemic Inflammation Response Index (SIRI) is an emerging prognostic marker for various malignant tumors, including GC. However, the mechanisms by which SIRI influences patient outcomes remain unclear. This study employed a multi-omics approach to analyze GC patients with different SIRI levels, aiming to identify factors underlying differences in prognosis. METHODS: A cohort of 495 GC patients was classified into high SIRI (n = 276) and low SIRI (n = 219) groups using a threshold of 2.6. Kaplan-Meier analysis and Receiver operating characteristic (ROC) curves were used to assess survival outcomes and the predictive accuracy of SIRI compared to other inflammatory markers. Gut microbiota and untargeted metabolomics analyses were conducted on stool samples from 45 GC patients, including 21 with high SIRI and 24 with low SIRI. RESULTS: Elevated SIRI levels were significantly associated with worse OS (P = 0.004, HR = 1.845, 95% CI: 1.231-2.766) and DFS (P < 0.0001, HR = 3.102, 95% CI: 2.016-4.772) in GC patients. Multi-omics analysis revealed distinct gut microbial and metabolic profiles between high- and low-SIRI subgroups. High SIRI was linked to increased Escherichia-Shigella and decreased levels of Blautia and Klebsiella. Metabolomic differences included elevated N-Acetylcadaverine and Epsilon-caprolactam, and decreased S-(PGA2)-glutathione. Integrative analysis identified significant microbe-metabolite correlations, such as Escherichia-Shigella with N-Acetylcadaverine and Epsilon-caprolactam. These findings suggest that SIRI-associated microbial and metabolic features may serve as non-invasive markers for inflammatory risk stratification in GC. CONCLUSION: High SIRI levels are associated with poorer prognosis in GC patients. Significant differences in gut microbiota and metabolites were observed across different SIRI levels in GC patients, showing their potential as non-invasive markers for GC risk stratification based on SIRI levels.