Immune cell death-related lncRNA signature as a predictive factor of clinical outcomes and immune checkpoints in gastric cancer

Abstract

Background: Immune cell death (ICD) is a type of tumor cell death that has recently been shown to activate and regulate tumor immunity. However, the role of ICD-related long non-coding RNAs (lncRNAs) in gastric cancer remains to be clarified. Methods: We obtained 375 tumor samples from the Cancer Genome Atlas (TCGA) database and randomly assigned them to training and verification groups. LASSO and Cox regression analysis were utilized to identify ICD-related lncRNAs and establish a risk model. The changes in the immune microenvironment of the two groups were compared by examining the tumor-infiltrating immune cells. Results: We established a tumor signature based on nine ICD-related lncRNAs. In light of the receiver operating characteristic and Kaplan-Meier curves, the prognostic values of this risk model were verified. Multivariate regression analysis showed that the risk score was an independent risk factor for the prognosis of patients in both the training cohort (HR 2.52; 95% CI: 1.65-3.87) and validation cohort (HR 2.70; 95% CI: 1.54-4.8). A nomogram was developed to predict the 1-, 3-, and 5-year survival of patients with gastric cancer, and the signature was linked to high levels of immunological checkpoint expression (B7-H3, VSIR). Conclusions: An ICD-related lncRNA signature could predict the immune response and prognosis of patients with gastric cancer. This prognostic signature could be employed to independently monitor the efficacy of immunotherapy for gastric cancer patients.

Keywords: gastric cancer; immune cell death; lncRNAs; prognostic signature; tumor immune microenvironment.