Development and Validation of a Robust Immune-Related Prognostic Signature for Gastric Cancer

Abstract

Background. An increasing number of reports have found that immune-related genes (IRGs) have a significant impact on the prognosis of a variety of cancers, but the prognostic value of IRGs in gastric cancer (GC) has not been fully elucidated. Methods. Univariate Cox regression analysis was adopted for the identification of prognostic IRGs in three independent cohorts (GSE62254, $n=300$ ; GSE15459, $n=191$ ; and GSE26901, $n=109$ ). After obtaining the intersecting prognostic genes, the three independent cohorts were merged into a training cohort ( $n=600$ ) to establish a prognostic model. The risk score was determined using multivariate Cox and LASSO regression analyses. Patients were classified into low-risk and high-risk groups according to the median risk score. The risk score performance was validated externally in the three independent cohorts (GSE26253, $n=432$ ; GSE84437, $n=431$ ; and TCGA, $n=336$ ). Immune cell infiltration (ICI) was quantified by the CIBERSORT method. Results. A risk score comprising nine genes showed high accuracy for the prediction of the overall survival (OS) of patients with GC in the training cohort ( $\text{AUC}>0.7$ ). The risk of death was found to have a positive correlation with the risk score. The univariate and multivariate Cox regression analyses revealed that the risk score was an independent indicator of the prognosis of patients with GC ( $p<0.001$ ). External validation confirmed the universal applicability of the risk score. The low-risk group presented a lower infiltration level of M2 macrophages than the high-risk group ( $p<0.001$ ), and the prognosis of patients with GC with a higher infiltration level of M2 macrophages was poor ( $p=0.011$ ). According to clinical correlation analysis, compared with patients with the diffuse and mixed type of GC, those with the Lauren classification intestinal GC type had a significantly lower risk score ( $p=0.00085$ ). The patients’ risk score increased with the progression of the clinicopathological stage. Conclusion. In this study, we constructed and validated a robust prognostic signature for GC, which may help improve the prognostic assessment system and treatment strategy for GC.