Abstract
Immune checkpoint blockade has attracted a lot of attention in the treatment of human malignant tumors. We are trying to establish a prognostic model of gastric cancer (GC) based on the expression profile of immunoregulatory factor-related genes. Based on the TCGA database, we identified 234 differentially expressed immunoregulatory factors. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) conducted enrichment analysis to clarify the biological functions of differential expression of immunoregulatory factors. STRING database predicted the interaction network between 234 differently expressed immune regulatory factors. The expression of 11 immunoregulatory factors was significantly related to the overall survival of gastric cancer patients. Univariate Cox regression analysis, Kaplan–Meier analysis and multivariate Cox regression analysis found that immunomodulatory factors were involved in the progression of gastric cancer and promising biomarkers for predicting prognosis. Among them, CXCR4 was related to the low survival of GC patients and a key immunomodulatory factor in GC. Based on TCGA data, the high expression of CXCR4 in GC was positively correlated with the advanced stage and grade of gastric cancer and related to poor prognosis. Univariate analysis and multivariate analysis indicated that CXCR4 was an independent prognostic indicator for TCGA gastric cancer patients. In vitro functional studies had shown that CXCR4 promoted the proliferation, migration, and invasion of gastric cancer cells. In summary, this study has determined the prognostic value of 11 immunomodulatory factors in gastric cancer. CXCR4 is an independent prognostic indicator for gastric cancer patients, which may help to improve the individualized prognostic prediction of GC and provide candidates for the diagnosis and treatment of GC.
Highlights
As one of the widely occurred carcinomas, gastric cancer (GC) is the third primary inducer of mortality amid cancers worldwide [1]
We identified 234 differentially expressed immunoregulatory factors with the criteria of the absolute logarithmic 2-fold change (FC) >1and the adjusted P-value of LIMMA
This study analyzed and constructed a gastric cancer prognosis model based on the expression profile of immunoregulatory factor-related genes, which provided new information for gastric cancer research
Summary
As one of the widely occurred carcinomas, gastric cancer (GC) is the third primary inducer of mortality amid cancers worldwide [1]. Despite the occurrence rate of GC has fallen sharply in western countries, it remains high in East Asian countries [2, 3]. This increasing trend of GC has decreased recently, especially the proportion of early GC cases. The primary contributor to the failure of GC treatment is drug resistance [6, 7]. Human CCR4 and CAF1 deacetylase mediate the regulation of human GC cell proliferation and tumorigenicity via modulating the cell cycle process [11]. Understanding the regulatory mechanism of GC will offer new insights into treating GC [12]
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