Immunogenic cell death related genes for predicting prognosis and drug sensitivity in gastric cancer

Abstract

Abstract Background: Immunogenic cell death (ICD), a specific type of regulated cell death, can trigger antitumor immune responses by inducing damage-associated molecular patterns. Determining the precise role of ICD in gastric cancer and how it can benefit patients in terms of predicting prognosis and efficacy could be of great value. Methods: We used the ESTIMATE immune score combined with a weighted gene co-expression network analysis to delineate ICD-associated gene modules and developed a predictive ICD risk model applicable to patients of any age, gender, and stage of gastric cancer. The prognoses and tumor microenvironment between the two groups were then compared. Finally, we assessed the capability of our risk signature to predict responses to immune checkpoint blockades (ICBs) and commonly used drugs. Results: In our ICD risk signature, nine ICD-related genes (PTTG1IP, TM2D1, LHX6, GLUD2, TIRAP, LIN7A, CAST, NKAPD1, and SWSAP1) were determined to be predictive markers. The risk score was calculated as follows: Risk score = (0.47124) × PTTG1IP + (-0.917) × TM2D1 + (0.67637) × LHX6 + (0.8493) × GLUD2 + (-1.1537) × TIRAP + (0.51718) × LIN7A + (0.71179) × CAST + (-0.7168) × NKAPD1 + (-0.8875) × SWSAP1.Patients with a low ICD score had longer overall survival, earlier clinical stages, lower immune cell infiltration, and less inhibitory receptor expression. Moreover, these patients responded better to ICBs and conventional chemotherapy. Conclusions: We established an ICD risk signature that could be used to predict prognosis and treatment efficacy in patients with gastric cancer. Our findings could shed light on fundamental ICD-relevant research and contribute to the development of precision therapies for patients with gastric cancer.