Background: To explore the hub gene closely related to the progression of gastric cancer (GC), so as to provide a theoretical basis for revealing the therapeutic mechanism of GC. Methods: The gene expression profile and clinical data of GSE15459 in Gene Expression Omnibus (GEO) database were downloaded. The weighted gene co-expression network analysis (WGCNA) was used to screen the key modules related to GC progression. Survival analysis was used to assess the influence of hub genes on patients' outcomes. CIBERSORT analysis was used to predict the tissue infiltrating immune cells in patients. Immunohistochemical staining was conducted to further verify the expression of hub genes. Results: Through WGCNA, a total of 26 co-expression modules were constructed, in which salmon module and royalblue module had strong correlation with GC progression. The results of enrichment analysis showed that genes in the two modules were mainly involved in toll-like receptor signaling pathway, cholesterol metabolism and neuroactive ligand-receptor interaction. Six hub genes (C1QA, C1QB, C1QC, FCER1G, FPR3 and TYROBP) related to GC progression were screened. Survival analysis showed overall survival in the high expression group was significantly lower than that in the low expression group. CIBERSORT analysis revealed that immune characteristics difference between patients in early stage and advanced stage. Immunohistochemical results confirmed that C1QB, FCER1G, FPR3 and TYROBP were significantly associated with disease progression in GC. Conclusion: Our study identified that C1QB, FCER1G, FPR3 and TYROBP played important roles in the progression of GC, and their specific mechanisms are worth further study.

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