Exploration of the Molecular Characteristics of the Tumor–Immune Interaction and Analysis of Immune Implication of CXCR4 in Gastric Cancer

Abstract Background:Gastric cancer (GC) is rated as one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths in the world. Despite the emergence of a combination of surgery, surveillance endoscopy, chemotherapy, radiotherapy, and various novel treatment strategies in recent years, the prognosis for patients with gastric cancer is far from optimistic due to its predisposition to invasion or metastasis and low rate of early diagnosis. GC exists in a complex tumor–immune microenvironment. Immune cell infiltration and tumor–immune molecules play a key role in tumor development and are closely related to the prognosis of patients. Therefore, understanding the cellular composition and function of TME is essential to grasp the tumor progression of GC, and is helpful to find molecular markers with the prognostic value that affect the immune response of GC patients.Methods:In this study, we performed multiple machine learning algorithms to identify immunophenotypes and immunological characteristics in GC patient’s data from the TCGA database and identified immune-related genes involved in the GC-immune interaction. In addition, we used R software and online databases to assess the status of lymphocytes and clarified the association between the hub gene and GC immunity, as well as the signaling pathways that regulate the immune response mediated by the hub gene.Results:In this study, we found a close linkage between CXCR4 and the immunity of GC. The CXCR4 gene expression was associated with immune cell infiltration levels and immunomodulators. We established an immune gene model for GC using CXCR4-associated immunomodulators. The risk scores derived from the gene signatures were significantly associated with survival in GC. And, our results demonstrated that the risk scores derived from CXCR4-associated immunomodulators could distinguish risk groups defined by differential expression of a set of signature genes.Conclusions: Our findings provided evidence of CXCR4's implication in tumor immunity, suggesting that CXCR4 may be a potential prognostic biomarker and immunotherapeutic target for GC. The prognostic immune markers from CXCR4-associated immunomodulators could independently predict the overall survival of GC. The prognostic immune model using CXCR4-associated immunomodulators contribute to the individualization of the clinical treatment strategy to improve the survival chances of patients.