We downloaded the mRNA expression profiles of patients with LUAD and corresponding clinical data from The Cancer Genome Atlas (TCGA) database and used the Least Absolute Shrinkage and Selection Operator Cox regression model to construct a multigene signature in the TCGA cohort, which was validated with patient data from the GEO cohort. Results showed differences in the expression levels of 120 necroptosis-related genes between normal and tumor tissues. An eight-gene signature (CYLD, FADD, H2AX, RBCK1, PPIA, PPID, VDAC1, and VDAC2) was constructed through univariate Cox regression, and patients were divided into two risk groups. The overall survival of patients in the high-risk group was significantly lower than of the patients in the low-risk group in the TCGA and GEO cohorts, indicating that the signature has a good predictive effect. The time-ROC curves revealed that the signature had a reliable predictive role in both the TCGA and GEO cohorts. Enrichment analysis showed that differential genes in the risk subgroups were associated with tumor immunity and antitumor drug sensitivity. We then constructed an mRNA-miRNA-lncRNA regulatory network, which identified lncRNA AL590666. 2/let-7c-5p/PPIA as a regulatory axis for LUAD. Real-time quantitative PCR (RT-qPCR) was used to validate the expression of the 8-gene signature. In conclusion, necroptosis-related genes are important factors for predicting the prognosis of LUAD and potential therapeutic targets.
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