A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma

Abstract

BackgroundGlioma is a highly aggressive brain cancer with a poor prognosis. Necroptosis is a form of programmed cell death occurring during tumor development and in immune microenvironments. The prognostic value of necroptosis in glioma is unclear. This study aimed to develop a prognostic glioma model based on necroptosis.MethodsA necroptosis-related risk model was constructed by Cox regression analysis based on The Cancer Genome Atlas (TCGA) training set, validated in two Chinese Glioma Genome Atlas (CGGA) validation sets. We explored the differences in immune infiltration and immune checkpoint genes between low and high risk groups and constructed a nomogram. Moreover, we compiled a third validation cohort including 43 glioma patients. The expression of necroptosis-related genes was verified in matched tissues using immunochemical staining in the third cohort, and we analyzed their relationship to clinicopathological features.ResultsThree necroptosis-related differentially expressed genes (EZH2, LEF1, and CASP1) were selected to construct the prognostic model. Glioma patients with a high risk score in the TCGA and CGGA cohorts had significantly shorter overall survival. The necroptosis-related risk model and nomogram exhibited good predictive performance in the TCGA training set and the CGGA validation sets. Furthermore, patients in the high risk group had higher immune infiltration status and higher expression of immune checkpoint genes, which was positively correlated with poorer outcomes. In the third validation cohort, the expression levels of the three proteins encoded by EZH2, LEF1, and CASP1 in glioma tissues were significantly higher than those from paracancerous tissues. They were also closely associated with disease severity and prognosis.ConclusionsOur necroptosis-related risk model can be used to predict the prognosis of glioma patients and improve prognostic accuracy, which may provide potential therapeutic targets and a theoretical basis for treatment.

A novel signature of cuproptosis-related lncRNAs predicts prognosis in glioma: Evidence from bioinformatic analysis and experiments

“…As far as we know, specific biomarkers for the treatment of gliomas based on CRLs have never been reported. In our current study, the CRL prognostic signature included 9 CRLs, which have been related to glioma growth and progression ( Yuan et al, 2022 ). HCG15 (human leukocyte antigen complex group 15) facilitates proliferation and invasion by enhancing ZNF641 transcription in hepatocellular carcinoma ( Yan et al, 2022b ).…”

“…It has been reported that pyroptosis ( Chen et al, 2021 ), necroptosis ( Liu et al, 2022a ; Yuan et al, 2022 ) and ferroptosis ( Wan et al, 2021 ) are pivotal in the development of glioma. For instance, genes associated with pyroptosis have been demonstrated to serve as prognostic indicators and signify the molecular characteristics of distinct subtypes of glioma ( Chen et al, 2021 ).…”

“…For instance, genes associated with pyroptosis have been demonstrated to serve as prognostic indicators and signify the molecular characteristics of distinct subtypes of glioma ( Chen et al, 2021 ). Further researches have indicated that genes related to necroptosis can act as predictive markers for glioma patients, resulting in an improved prognostic precision ( Liu et al, 2022a ; Yuan et al, 2022 ). Additionally, a novel risk score connected with ferroptosis-related genes has been reported to possess the capability of predicting the prognosis and immunotherapy outcomes of patients with glioma ( Wan et al, 2021 ).…”

“…Additionally, a novel risk score connected with ferroptosis-related genes has been reported to possess the capability of predicting the prognosis and immunotherapy outcomes of patients with glioma ( Wan et al, 2021 ). Recently, a study has described cuproptosis ( Tsvetkov et al, 2022 ), an alternative form of cell death in comparison to pyroptosis, necroptosis and ferroptosis ( Chen et al, 2021 ; Wan et al, 2021 ; Liu et al, 2022a ; Yuan et al, 2022 ). Copper can regulate intracellular homeostasis as a co-factor for multiple enzymes, but excessive copper accumulation may prove harmful and ultimately result in cell death ( Kim et al, 2008 ).…”

A novel TRP channel-related prognostic model of glioma based on transcriptomics and single cell sequencing analysis

“…The prognostic value of a single biomarker is very limited, and integrating multiple biomarkers into one model can improve the prediction e ciency and accuracy (23). For example, a study constructed a prognostic model for glioma patients based on three necroptosis-related genes, and high-risk patients had higher immune in ltration rates and immune checkpoint genes expression than low-risk patients, which were positively associated with poor prognosis (24). Another study constructed a prognostic model in patients with LGG based on cellular senescence-related genes and found that for patients, cellular senescence-related scores could be used as an independent predictor, and patients with high scores had a worse prognosis.…”