Necroptosis-related Prognostic Gene Signature to Aid Therapy in Lung Adenocarcinoma

Lung adenocarcinoma (LUAD) is the most common type of non-small cell lung cancer (NSCLC), which is also the most important cause of cancer-related deaths. 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 tumor, but the prognostic role and biological functions of necroptosis in LUAD are still obscure. In this study, we constructed a prognostic Necroptosis-related gene (NRG) 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 characteristics information. Next, Kaplan-Meier analysis, receiver operating characteristic (ROC), univariate Cox and multivariate Cox regression were made to validate and evaluate the model. We also accurately and quantitatively predicted the prognosis of LUAD patients using our nomogram, which includes age, gender, stage and risk score. To improve patients’ prognosis and achieve personalized precision medicine, we analyzed the immune landscape in LUAD and predicted the sensitivity of LUAD patients with different risk scores to immunotherapeutic regimens and chemotherapeutic regimens. In conclusion, our study provides a reference for in-depth mechanistic exploration of necroptosis in LUAD.