Abstract

BackgroundChronic inflammation and immune cell dysfunction in the tumor microenvironment are key factors in the development and progression of gastric tumors. However, inflammation-related genes associated with gastric cancer prognosis and their relationship with the expression of immune genes are not fully understood.MethodIn this study, we established an inflammatory response model score called “Riskscore”, based on differentially expressed genes in gastric cancer. We used Survival and Survminer packages in R to analyze patient survival and prognosis in risk groups. The survival curve was plotted using the Kaplan–Meier method, and the log-rank test was used to assess statistical significance, and we performed the ROC analysis using the R language package to analyze the 1-, 3-, and 5-year survival of patients in the GEO and TCGA databases. Single-factor and multi-factor prognostic analyses were carried out for age, sex, T, N, M, and risk score. Pathway enrichment analysis indicated immune factor-related pathway enrichment in both patient groups. Next, we screened for important genes that are involved in immune cell regulation. Finally, we created a correlation curve to explore the correlation between Riskscore and the expression of these genes.ResultsThe prognosis was significantly different between high- and low-risk groups, and the survival rate and survival time of the high-risk group were lower than those of the low-risk group. we found that the pathways related to apoptosis, hypoxia, and immunity were most enriched in the risk groups. we found two common tumor-infiltrating immune cell types (i.e., follicular helper T cells and resting dendritic cells) between the two risk groups and identified 10 genes that regulate these cells. Additionally, we found that these 10 genes are positively associated with the two risk groups.ConclusionFinally, a risk model of the inflammatory response in gastric cancer was established, and the inflammation-related genes used to construct the model were found to be directly related to immune infiltration. This model can improve the gastric cancer prognosis prediction. Our findings contribute to the development of immunotherapy for the treatment of gastric cancer patients.

Highlights

  • In 2017, 1.2 million patients were diagnosed with gastric cancer (GC) and there were 865,000 reported deaths worldwide

  • Previous studies have shown that inflammation and immunity play important roles in the tumor microenvironment

  • To explore the relationship between inflammation, immunity, and gastric cancer, we downloaded gene ontology (GO) datasets from the Gene Set Enrichment Analysis (GSEA) website to extract genes related to the inflammatory response

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Summary

Introduction

In 2017, 1.2 million patients were diagnosed with gastric cancer (GC) and there were 865,000 reported deaths worldwide. In China, gastric cancer is of particular concern as it was the second leading cause of cancer-related deaths in 2015 [2]. All of the cells that reside in the tumor microenvironment take part in the formation and development of tumors [4, 5]. Studies have shown that chronic inflammation contributes to cancer progression [6]. Chronic inflammation and immune cell dysfunction in the tumor microenvironment are key factors in the development and progression of gastric tumors. Inflammation-related genes associated with gastric cancer prognosis and their relationship with the expression of immune genes are not fully understood

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