Establishment and Analysis of an Individualized Immune-Related Gene Signature for the Prognosis of Gastric Cancer.

Mengying Li,Yaxin Chen,Bingqian Huang,Jiawei Zhang,Wei Cao,Guodong Cao,Zhipeng Zhu,Bo Chen

doi:10.3389/fsurg.2022.829237

Abstract

A growing number of studies have shown that immunity plays an important clinical role in the process of gastric cancer (GC). The purpose of this study was to explore the function of differentially expressed immune-related genes (DEIRGs) of GC, and construct a gene signature to predict the overall survival (OS) of patients. Gene expression profiles and clinical data of GC patients were downloaded from TCGA and GEO databases. Combined with immune-related genes (IRGs) downloaded from the ImmPort database, 357 DEIRGs in GC tissues and adjacent tissues were identified. Based on the analysis of Lasso and Cox in the training set, a prognostic risk scoring model consisting of 9 (RBP7, DES, CCR1, PNOC, SPP1, VIP, TNFRSF12A, TUBB3, PRKCG) DEIRGs was obtained. Functional analysis revealed that model genes may participate in the formation and development of tumor cells by affecting the function of cell gap junction intercellular communication (GJJC). According to the model score, the samples were divided into high-risk and low-risk groups. In multivariate Cox regression analysis, the risk score was an independent prognostic factor (HR = 1.674, 95% CI = 1.470–1.907, P < 0.001). Survival analysis showed that the OS of high-risk GC patients was significantly lower than that of low-risk GC patients (P < 0.001). The area under the receiver operating characteristic curve (ROC) of the model was greater than other clinical indicators when verified in various data sets, confirming that the prediction model has a reliable accuracy. In conclusion, this study has explored the biological functions of DEIRGs in GC and discovered novel gene targets for the treatment of GC. The constructed prognostic gene signature is helpful for clinicians to determine the prognosis of GC patients and formulate personalized treatment plans.

Highlights

Gastric cancer (GC) is the fifth most common cancer and the third most common cause of cancer death worldwide [1], and is one of the most common malignant tumors of the digestive system [2]
In R language, 357 differentially expressed immune-related genes (DEIRGs) were obtained by intersection of immune-related genes (IRGs) and all Differentially expressed genes (DEGs), including 204 upregulated DEIRGs and 153 down-regulated DEIRGs
According to the risk value calculated by the model, patients are divided into high and low risk groups, we found that the risk score calculated based on 9-gene signature was found to be significantly correlated with the infiltration of 9 types of immune cells, including Plasma cells, T cells regulatory (Tregs), Macrophages M0, etc. (Figures 11A,B)

Summary

Introduction

Gastric cancer (GC) is the fifth most common cancer and the third most common cause of cancer death worldwide [1], and is one of the most common malignant tumors of the digestive system [2]. Most GC patients have reached the stage of inoperable radical treatment at the time of diagnosis. Tumor pathology (T), lymph node biopsy (N) and distant organ metastasis (M) are the main criteria to determine the prognosis of patients at present, but the prognosis of patients under the same TNM stage is very different [4]. It has been observed that the prognosis of GC is related to the pathological stage, and the tumor immune state may have an important influence on the prognosis of patients [5]

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