Abstract
Immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer (GC). The research on tumor infiltrating immune cells (TIICs) and immune-related genes in the tumor microenvironment (TME) greatly encourages the development of immunotherapy. The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 TIICs based on gene expression profiles of GC tissues, which were downloaded from TCGA and GEO. TCGA was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes. We have observed the enrichment of multiple TIICs in microenvironment of GC. Some of these cells were closely related to tumor mutational burden (TMB), microsatellite instability (MSI), Fuhrman grade, and TNM staging. Survival analysis showed that the infiltration level of CD8+ T cells, activated CD4+ memory T cells and M2 macrophages were significantly related to the prognosis of GC patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules. The expression levels of CALCR and PTH1R are strikingly related to the expression of immune checkpoint and the prognosis of GC patients. The type and number of TIICs in microenvironment of GC, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment.
Highlights
Gastric cancer (GC) remains an important cancer worldwide and is responsible for over one million new cases in 2020 and an estimated 769,000 deaths, ranking fifth for incidence and fourth for mortality globally (Sung et al, 2021)
The existing immune efficacy markers can be roughly divided into two categories: the first category is molecular markers related to tumor neoantigen load, such as microsatellite instability (MSI) or tumor mutational burden (TMB) increase; The second category is related to the tumor microenvironment (TME), including the expression of programmed death ligand 1 (PD-L1) protein, tumor cell infiltration, and copy number variation (Cristescu et al, 2018)
We first revealed the infiltration of 22 tumor infiltrating immune cells (TIICs) in gastric cancer (GC), and subsequently we investigated the difference between tumor tissues and normal tissues using the CIBERSORT algorithm
Summary
Gastric cancer (GC) remains an important cancer worldwide and is responsible for over one million new cases in 2020 and an estimated 769,000 deaths, ranking fifth for incidence and fourth for mortality globally (Sung et al, 2021). The existing immune efficacy markers can be roughly divided into two categories: the first category is molecular markers related to tumor neoantigen load, such as microsatellite instability (MSI) or tumor mutational burden (TMB) increase; The second category is related to the tumor microenvironment (TME), including the expression of PD-L1 protein, tumor cell infiltration, and copy number variation (Cristescu et al, 2018). These two types of markers are involved in the different stages of tumor immunotherapy and form a unified whole. The immunotherapy of GC is still at an early stage, and more research is needed to provide a theoretical basis for its development
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