Necroptosis-related lncRNAs signature predicts prognosis and influences immune microenvironment in patients with colon adenocarcinoma

Abstract

Abstract Background: The present study aimed to identify an NRLs (necroptosis-related long noncoding RNAs [lncRNAs]) signature for the prognosis of colon adenocarcinoma (COAD) and to investigate its potential relationship with clinical characteristics and immune microenvironment. Methods:Clinical information of patients with COAD and RNA sequence data were downloaded from The Cancer Genome Atlas (TCGA) database. Necroptosis-related genes (NRGs) were obtained from the GeneCards website. Co-expression analysis was performed to identify NRLs. By using the “limma” package in R software, differentially expressed NRLs (DE-NRLs) were screened from the identified NRLs. A prognostic NRLs signature was established based on the results of univariate Cox regression analysis, LASSO algorithm, and multivariate Cox analysis. Survival analysis and area under the curve (AUC) of receiver operating characteristic (ROC) were used to evaluate the prognostic efficacy of this signature. Clinical correlation and independent prognostic factors were then assessed, and a predictive nomogram was then constructed. Finally, gene set enrichment analysis (GSEA) was conducted to determine the potential molecular mechanisms. Immune analysis was performed to analyze the tumor microenvironment and to predict the immune response of patients with COAD. Lastly, experiments were conducted to validate the expression and function of NRLs involved in the prognostic signature. Results: Three NRLs were identified, and a prognostic signature was constructed from them. According to the risk score calculated using this signature, patients were classified into high-risk and low-risk groups. The signature exhibited a strong ability to predict survival, and the risk score was confirmed as an independent prognostic factor. GSEA showed differences in specific molecular pathways involved in immune response, mitochondrial function, and energy metabolism. The two groups also showed significant differences in immune cell infiltration, immune function, and immune checkpoint gene expression. The high-risk group showed higher immunogenicity and may benefit from immunotherapy. Lastly, in vivo experiments validated the expression and function of NRLs involved in the prognostic signature. Conclusions:The prognostic signature of NRLs developed in this study can facilitate the clinical diagnosis and treatment of patients with COAD and may serve as a valuable reference for in-depth studies of functional mechanisms of NRLs in the immune microenvironment.