Abstract
BackgroundGastric cancer (GC) is one of the high-risk cancers that lacks effective methods for prognosis prediction. Therefore, we searched for immune cells related to the prognosis of GC and studied the role of related genes in GC prognosis.MethodsIn this study, we collected the mRNA data of GC from The Cancer Genome Atlas (TCGA) database and studied the immune cells that were closely related to the prognosis of GC. Spearman correlation analysis was performed to show the association between immune cell-related genes and the differentially expressed genes (DEGs) of GC. Univariate and multivariate Cox regression analyses were conducted on the immune cell-related genes with a high correlation with GC. A prognostic risk score model was constructed and the most significant feature genes were identified. Kaplan–Meier method was then used to compare the overall survival (OS) of patients with high-risk and low-risk, and receiver operating characteristic (ROC) analysis was used to assess the accuracy of the risk model. In addition, GC patients were grouped according to the median expression of the features genes, and survival analysis was further carried out.ResultsIt was noted that regulatory T cells (Tregs) were significantly correlated with the prognosis of GC, and 172 genes related to Tregs were found to be closely associated with GC. An optimal prognostic risk model was constructed, and a 5-gene (including LRFN4, ADAMTS12, MCEMP1, HP and MUC15) signature-based risk score was established. Survival analysis showed significant difference in OS between low-risk and high-risk samples. ROC analysis results indicated that the risk model had a high accuracy for the prognosis prediction of samples (AUC = 0.717). The results of survival analysis on each feature gene based on expression levels were consistent with the results of multivariate Cox analysis for predicting the risk rate of the 5 genes.ConclusionThese results proved that the 5-gene signature-based risk score could be used to predict the survival of GC patients, and these 5 genes were closely related to Tregs. These findings are of great significance for studying the role of immune cells and related immune factors in regulating the prognosis of GC.
Highlights
Gastric cancer (GC) is one of the high-risk cancers that lacks effective methods for prognosis prediction
In order to study the differences in the infiltration level of immune cells between GC tumor and normal tissues, mRNA expression data from 407 GC samples in The Cancer Genome Atlas (TCGA)-STAD dataset were used to generate infiltration levels of 22 major immune cells in each sample using the CIBERSORT algorithm (Fig. 2a)
The data were processed by clustering analysis and the samples were divided into Normal group and Tumor group to compare the infiltration level (Fig. 2b)
Summary
Gastric cancer (GC) is one of the high-risk cancers that lacks effective methods for prognosis prediction. Recent experiments of drugs acting on immunomodulatory pathways have shown that when disease-related immune pathways are modulated, they will regulate immune response of patients, which will extend the survival time of patients with a variety of cancers, including melanoma, non-small cell lung cancer (NSCLC), renal cell cancer and GC [13, 16]. Some immune factors, such as PD-L1 and tumor-infiltrating lymphocytes, have been proved to have significant immunological effects on GC [17,18,19]. Analyzing and searching for immune cells and immune cytokines associated with the prognosis of GC is the key of immunotherapy
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