Identification of Necroptosis-Related Genes in Lung Adenocarcinomas: A Novel Prognostic Model

Abstract

Objective: Necroptosis is closely related to tumor occurrence and metastasis, but the research on Lung Adenocarcinoma (LUAD) is unclear. We aimed to construct a model for LUAD patients’ prognosis prediction based on necroptosis-associated genes. Methods: We collected the Gene profiles of LUAD patients from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The identification of differentially expressed genes (DEGs) associated with necroptosis and the construction of the prognosis models were performed using Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analyses. The relationship between necroptosis pathways and LUAD was identified using the protein-protein interaction (PPI) network and functional enrichment analyses. Predictive and prognostic values of models were assessed using Cox proportional hazards regression. Finally, we used Quantitative verification of differential genes by Real Time Quantitative PCR (RT-qPCR) to verify the differential gene expression in A549 and normal cells. Results: We constructed a model including seven necroptosis-related genes (FADD, PLK1, PANX1, BIRC2, HSPA4, ID1, and HSP90AA1) for the prognosis and survival prediction of LUAD patients. Patients were stratified according to the risk score, and those with a high-risk score showed poorer outcomes when compared to low-risk patients. Functional enrichment analyses showed that the function of necroptosis in LUAD was mainly concentrated in cell mitosis, neurotransmitter transmission, and drug metabolism. Compared with other clinical factors, the prognosis model better predicted the prognosis (AUC (Area Under roc Curve) = 0.718). The model’s accuracy was confirmed in an independent verification set GSE (GEO (Gene Expression Omnibus) Series) 31210 (p < 0.0001). Finally, RT-qPCR confirmed the high expression of genes in the model in A549 cells, which was consistent with the trend of gene expression in the dataset. Conclusions: Our prognostic model can independently and accurately predict the prognosis of LUAD patients, which helps to clarify the link between necroptosis.