Prognostic necroptosis-related gene signature aids immunotherapy in lung adenocarcinoma

Background: Necroptosis is a phenomenon of cellular necrosis resulting from cell membrane rupture by the corresponding activation of Receptor Interacting Protein Kinase 3 (RIPK3) and Mixed Lineage Kinase domain-Like protein (MLKL) under programmed regulation. It is reported that necroptosis is closely related to the development of tumors, but the prognostic role and biological function of necroptosis in lung adenocarcinoma (LUAD), the most important cause of cancer-related deaths, is still obscure. Methods: In this study, we constructed a prognostic Necroptosis-related gene signature based on the RNA transcription data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases as well as the corresponding clinical information. Kaplan-Meier analysis, receiver operating characteristic (ROC), and Cox regression were made to validate and evaluate the model. We analyzed the immune landscape in LUAD and the relationship between the signature and immunotherapy regimens. Results: Five genes (RIPK3, MLKL, TLR2, TNFRSF1A, and ALDH2) were used to construct the prognostic signature, and patients were divided into high and low-risk groups in line with the risk score. Cox regression showed that risk score was an independent prognostic factor. Nomogram was created for predicting the survival rate of LUAD patients. Patients in high and low-risk groups have different tumor purity, tumor immunogenicity, and different sensitivity to common antitumor drugs. Conclusion: Our results highlight the association of necroptosis with LUAD and its potential use in guiding immunotherapy.