Construction and Validation of a Necroptosis-Related lncRNA Signature in Prognosis and Immune Microenvironment for Glioma

Abstract

Background. Glioma is the most common primary brain tumor, representing approximately 80.8% of malignant tumors. Necroptosis triggers and enhances antitumor immunity and is expected to be a new target for tumor immunotherapy. The effectiveness of necroptosis-related lncRNAs as potential therapeutic targets for glioma has not been elucidated. Methods. We acquired RNA-seq data sets from LGG and GBM samples, and the corresponding clinical characteristic information is from TCGA. Normal brain tissue data is from GTEX. Based on TCGA and GTEx, we used univariate Cox regression to sort out survival-related lncRNAs. Lasso regression models were then built. Then, we performed a separate Kaplan-Meier analysis of the lncRNAs used for modeling. We validated different risk groups via OS, DFS, enrichment analysis, comprehensive immune analysis, and drug sensitivity. Results. We constructed a 12 prognostic lncRNAs model after bioinformatic analysis. Subsequently, the risk score of every glioma patient was calculated based on correlation coefficients and expression levels, and the patients were split into low- and high-risk groups according to the median value of the risk score. A nomogram was established for every glioma patient to predict prognosis. Besides, we found significant differences in OS, DFS, immune infiltration and checkpoints, and immune therapy between different risk subgroups. Conclusion. Predictive models of 12 necroptosis-related lncRNAs can facilitate the assessment of the prognosis and molecular characteristics of glioma patients and improve treatment modalities.

Necroptosis-related lncRNAs: establishment of a gene module and distinction between the cold and hot tumors in glioma

“…Due to their abnormal expression in glioma patients' brain tissue, cerebrospinal fluid, or peripheral circulation, some lncRNAs are thought to be potential biomarkers. Just recently, some necroptosis-related lncRNAs have also been identified which could be used to assess the prognosis and molecular characteristics of glioma (18)(19)(20). However, it is unknown if these lncRNAs are implicated in distinct glioma immune microenvironments or if they may be exploited as novel markers to distinguish cool from hot tumors and as prospective immunotherapy targets for glioma.…”

Regulated cell death in glioma: promising targets for natural small-molecule compounds

“…Some scientists have found predictive models for 12 lncRNAs to help assess glioma patients’ prognosis and molecular characteristics. For example, GSEA-GO is associated with Wnt, inositol phosphate metabolism, butyrate metabolism, long-term depression, and taste transduction, improving treatment modality and potentially stimulating future exploration of glioma formation and treatment ( 32 ). Search for specific biomarkers based on markers of necroptosis may be more precise and effective in LGG and GBM management, which may provide new clues for immunotherapy and prognosis.…”

A novel disulfidptosis-related lncRNA signature predicts prognosis and therapeutic response in low-grade glioma

“…Long noncoding RNAs (lncRNAs), which are > 200 nucleotides in length and have limited protein-coding potential, play an indispensable role in regulating the expression of various cancer-associated genes through various mechanisms, including translation, histone modi cation, post-transcriptional processes, cancer stem cell function, and epithelial-mesenchymal transition [10][11] . Furthermore, numerous studies have reported that lncRNAs are associated with tumor progression and prognosis in patients with LGG [12][13][14][15][16][17][18] .…”