Background. Gastric cancer (GC) has been divided into four molecular subtypes, of which the mesenchymal subtype has the poorest survival. Our goal is to develop a prognostic signature by integrating the immune system and molecular modalities involved in the mesenchymal subtype. Methods. The gene expression profiles collected from 6 public datasets were applied to this study, including 1,221 samples totally. Network analysis was applied to integrate the mesenchymal modalities and immune signature to establish an immune-based prognostic signature for GC (IPSGC). Results. We identified six immune genes as key factors of the mesenchymal subtype and established the IPSGC. The IPSGC can significantly divide patients into high- and low-risk groups in terms of overall survival (OS) and relapse-free survival (RFS) in discovery (OS: ) and 5 independent validation sets (OS range: to ; RFS range: to ). Further, in multivariate analysis, the IPSGC remained an independent predictor of prognosis and performed better efficiency compared to clinical characteristics. Moreover, macrophage M2 was significantly enriched in the high-risk group, while plasma cells were enriched in the low-risk group. Conclusions. We propose an immune-based signature identified by network analysis, which is a promising prognostic biomarker and help for the selection of GC patients who might benefit from more rigorous therapies. Further prospective studies are warranted to test and validate its efficiency for clinical application.
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