Identification and Validation of a Novel Necroptosis-Related Long Noncoding RNA Prognostic Signature for Lung Adenocarcinoma

Abstract

Background. Several cancers, including lung adenocarcinoma (LUAD), are caused by genes related to necroptosis. However, it is still unknown how necroptosis-related long noncoding RNAs (lncRNAs) may be involved in LUAD. In order to predict the prognosis of LUAD patients and personalize immunotherapy, this study set out to construct a necroptosis-related lncRNA prognostic signature (NLPS). Methods. The Cancer Genome Atlas (TCGA) database was used to download the LUAD transcriptome data and the associated clinical data. lncRNAs associated with necroptosis were screened using coexpression analysis. An NLPS was built using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The Gene Expression Omnibus (GEO) database’s GSE30219 was used to validate the NLPS. The prognostic value of the risk score was assessed using Kaplan-Meier survival, receiver operating characteristic (ROC) Cox regression, multivariate Cox regression, and nomogram analyses. Then, we looked into the differences between the low- and high-risk groups in the tumor immune microenvironment, immunotherapy response, and half-maximal inhibitory concentration (IC50). Results. The 14 lncRNAs in a novel NLPS were created. With further validation in the GSE30219 dataset, the risk score according to the NLPS was an independent prognostic indicator for LUAD patients. Patients with better overall survival (OS) in the low-risk group, who were characterized by increased immune cell infiltration, tumor mutational burden (TMB), and immunophenoscore (IPS), may have hot tumors and higher immunotherapy response rates. In addition, the risk score was also closely linked to sensitivity to various anticancer medications. Conclusions. We constructed a novel NLPS that could predict OS and sensitivity to immunotherapy in LUAD patients.

Integrated bioinformatics analysis of noncoding RNAs with tumor immune microenvironment in gastric cancer

“…LncRNAs have been implicated in facilitating the evasion of immune surveillance by tumor cells through multiple mechanisms, including the promotion of an immunosuppressive microenvironment 26 – 28 . Multiple studies used comprehensive analysis to determine the functions of various lncRNAs in tumor immune microenvironment (TIME) in various cancers, such as colon cancer 29 , clear cell renal cell carcinoma 30 , breast cancer 31 , 32 , lung cancer 33 , 34 , thyroid cancer 35 , adrenocortical adenocarcinoma 36 , bladder cancer 37 , and head and neck squamous cell carcinoma 38 . LncRNA NKILA has demonstrated the ability to initiate apoptosis in tumor-specific T cells, thereby impeding their capacity to infiltrate the tumor, leading to tumor immune evasion 39 .…”

Genomic analysis of TNF-related genes with prognosis and characterization of the tumor immune microenvironment in lung adenocarcinoma

“…A recent study predicted the prognosis signature of Necroptosis-Related long noncoding RNA in LUAD patients (29), the AUCs of the signature in the validation cohorts were 0.609, 0.618, and 0.631 at 1, 3,5 years, respectively; in contrast, those determined by the model in the present work were 0.698, 0.657, 0.67 at 1, 3, 5 years, respectively, suggesting a slightly better predictability and stability of the proposed model. However, this study has certain limitations.…”