AUTHOR=Wu Jie , Song Dingli , Zhao Guang , Chen Sisi , Ren Hong , Zhang Boxiang 

TITLE=Cross-talk between necroptosis-related lncRNAs to construct a novel signature and predict the immune landscape of lung adenocarcinoma patients

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.966896

DOI=10.3389/fgene.2022.966896

ISSN=1664-8021

ABSTRACT=Background: As a new style of cell death, necroptosis plays crucial role in tumor immune microenvironment. LncRNAs have been identified to act as competitive RNAs to influence genes involved in necroptosis. Therefore, we aim to creat a signature based on necroptosis-related lncRNAs to predict the prognosis and immune landscape of Lung Adenocarcinoma (LUAD) Patients in this study.
Methods: TCGA database were used to acquire RNA sequencing (RNA-Seq) data and clinical information of 59 lung normal samples and 535 lung adenocarcinoma samples. The least absolute shrinkage and selection operator (LASSO) cox regression was performed to construct the prognostic NRGs-lncRNA signature. Then we used Kaplan-Meier (K-M) analysis, time-dependent ROC curves, univariate and multivariate cox regression analysis and nomogram to validate this signature. In addition, GO, KEGG, and GSVA were analyzed to investigate the potential molecular mechanism. Moreover, we analyaed the relationship between our identified signature and immune microenvironment, TMB, and some clinical characteristics. At last, we detected the expression of the six Necroptosis-Related lncRNAs in BEAS-2B and LUAD cells.
Results: We constructed a NRGs-lncRNA signature consist of six lncRNAs (FRMD6-AS1, LINC01480, FAM83A-AS1, FRMD6-AS1, MED4-AS1, and LINC01415) in LUAD. LUAD patients with high risk score had a lower chance of survival with an AUC of 0.739, 0.709 and 0.733 in 1-year, 3-year, and 5-year respectively. The results based on GO, KEGG, and GSVA enrichment analysis demonstrated that NRGs-lncRNA signature-related genes was mainly correlated with immune pathways, metabolic- and cell growth-related pathways, cell cycle, and apoptosis. Moreover, the risk score was  correlated with the immune status of LUAD patients. Patients with higher risk score had lower ESTIMATE score and higher TIDE score. And the risk score was positively correlated with TMB. LINC01480, FRMD6-AS1 and FAM83A-AS1 was significantly overexpressed in lung adenocarcinoma cells, while the expression level of MED4-AS1 and LINC01415 was lower in lung adenocarcinoma cells.
Conclusions: Overall, an innovative prognostic signature based on NRGs-lncRNAs was developed for LUAD through comprehensive bioinformatics analysis, which can act as a predictor of immunotherapy and may provide guidance for clinicians.