Construction and validation of a prognosis signature based on the immune microenvironment in gastric cancer

Li-Hong Wu; Xiang-Xu Wang; Yan Wang; Jing Wei; Zi-Rong Liang; Xi Yan; Jun Wang

doi:10.3389/fsurg.2023.1088292

Construction and validation of a prognosis signature based on the immune microenvironment in gastric cancer

Front Surg. 2023 Mar 31:10:1088292. doi: 10.3389/fsurg.2023.1088292. eCollection 2023.

Authors

Li-Hong Wu¹, Xiang-Xu Wang², Yan Wang¹, Jing Wei¹, Zi-Rong Liang¹, Xi Yan¹, Jun Wang¹

Affiliations

¹ Xijing 986 Hospital Department, Fourth Military Medical University, Xi'an, China.
² Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Abstract

Background: Gastric cancer (GC) is an aggressive malignant tumor with a high degree of heterogeneity, and its immune microenvironment is closely associated with tumor growth, development and drug resistance. Therefore, a classification system of gastric cancer based explicitly on the immune microenvironment context might enrich the strategy for gastric cancer prognosis and therapy.

Methods: A total of 668 GC patients were collected from TCGA-STAD (n = 350), GSE15459 (n = 192), GSE57303 (n = 70) and GSE34942 (n = 56) datasets. Three immune-related subtypes (immunity-H, -M, and -L) were identified by hierarchical cluster analysis based on the ssGSEA score of 29 immune microenvironment-related gene sets. The immune microenvironment-related prognosis signature (IMPS) was constructed via univariate Cox regression, Lasso-Cox regression and multivariate Cox regression, and nomogram model combining IMPS and clinical variables was further constructed by the "rms" package. RT-PCR was applied to validate the expression of 7 IMPS genes between two human GC cell lines (AGS and MKN45) and one normal gastric epithelial cell line (GES-1).

Results: The patients classified as immunity-H subtype exhibited highly expressed immune checkpoint and HLA-related genes, with enriched naïve B cells, M1 macrophages and CD8 T cells. We further constructed and validated a 7-gene (CTLA4, CLDN6, EMB, GPR15, ENTPD2, VWF and AKR1B1) prognosis signature, termed as IMPS. The patients with higher IMPS expression were more likely to be associated with higher pathology grade, more advanced TNM stages, higher T and N stage, and higher ratio of death. In addition, the prediction values of the combined nomogram in predicting 1-year (AUC = 0.750), 3-year (AUC = 0.764) and 5-year (AUC = 0.802) OS was higher than IMPS and individual clinical characteristics.

Conclusions: The IMPS is a novel prognosis signature associated with the immune microenvironment and clinical characteristics. The IMPS and the combined nomogram model provide a relatively reliable predictive index for predicting the survival outcomes of gastric cancer.

Keywords: gastric cancer; immune microenvironment; nomogram; prognosis signature; ssGSEA analysis.