Impact of Macrophage-Associated Hallmark Genes on Patient Prognosis and the Immune microenvironment in Gastric Cancer

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. The interaction between macrophages and other cells as well as the immune microenvironment plays a key role in the progression and prognosis of gastric cancer. However, the molecular mechanisms linking macrophages with gastric cancer prognosis and immune microenvironment remain to be explored. Bioinformatics analysis was utilized to identify differentially expressed genes between the GC group and the control group. Then, the prognostic genes were selected to construct a risk model, and the patients were divided into high- and low-risk groups. Kaplan-Meier survival analysis was used to compare the prognosis of the two groups. The results showed that GPX3, SERPINE1, and SPARC were identified as prognostic genes, and GC patients were divided into high-risk and low-risk groups according to the risk score. KM curve showed that the survival time of high-risk group was shorter, and age and N/M stage were independent prognostic factors. Immune infiltration analysis showed that CPA3/SPARC was positively correlated with plasma cells and negatively correlated with M0 macrophages. Regulatory network analysis revealed that HOXB6 and ZEB1 regulated SERPINE1 and SPARC, while SOX7 and AHR regulated SERPINE1 and GPX3. Studies have confirmed the key role of macrophage-associated gene signatures and the immune microenvironment in predicting the prognosis of patients with GC. The constructed risk model has a strong predictive ability. This regulatory network provides new insights into immune regulation and potential therapeutic targets for the treatment of gastric cancer.