Identification of necroptosis-related signature and tumor microenvironment infiltration characteristics in lung adenocarcinoma

Abstract

Objectives

Lung cancer remains the most common cancer and the leading cause of cancer deaths. However, the potential roles of necroptosis-related signature and tumor microenvironment (TME) in the lung adenocarcinoma (LUAD) still unknown.

Materials and methods

Expression data and clinical information were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. In the TCGA dataset, necroptosis phenotype-related differentially expressed genes (DEGs) were identified. A necroticscore score was developed and validated by integrating GEO-meta datasets. The clinical value of the risk score was further evaluated using Kaplan-Meier and immunotherapeutic cohort (IMvigor210 cohort).

Results

Three necroptosis-related patterns and distinct necroptosis-related gene cluster were identified based on the abnormal expression of 14 necroptosis regulators. The necroptosis genomic phenotypes were obtained based on 117 necroptosis phenotype-related DEGs. A necroticscore were constructed to evaluate necroptosis pattern of each patient. Low necroticscore was linked with decreased immune check-point expression, enhanced immune check-point inhibitor response, and better clinical benefits.

Conclusion

This study suggested that the crucial roles of necroptosis-related regulators in modeling the heterogeneity of TME characteristics. Thus, assessing necroptosis patterns provided us with a deeper understanding of TME and might guide the clinical immunotherapy treatment of lung cancer.