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

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 mod...

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Main Authors: Ying-Shi Yuan, Xin Jin, Lu Chen, Jia-Min Liao, Yang Zhang, Ke-Wei Yu, Wei-Kang Li, Shun-Wang Cao, Xian-Zhang Huang, Chun-Min Kang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.1027794/full
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author Ying-Shi Yuan
Ying-Shi Yuan
Xin Jin
Lu Chen
Jia-Min Liao
Yang Zhang
Ke-Wei Yu
Wei-Kang Li
Shun-Wang Cao
Xian-Zhang Huang
Xian-Zhang Huang
Chun-Min Kang
Chun-Min Kang
author_facet Ying-Shi Yuan
Ying-Shi Yuan
Xin Jin
Lu Chen
Jia-Min Liao
Yang Zhang
Ke-Wei Yu
Wei-Kang Li
Shun-Wang Cao
Xian-Zhang Huang
Xian-Zhang Huang
Chun-Min Kang
Chun-Min Kang
author_sort Ying-Shi Yuan
collection DOAJ
description 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.
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spelling doaj.art-8d1ed84e8078406082909cf89e861a8b2022-12-22T04:06:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10277941027794A novel model based on necroptosis-related genes for predicting immune status and prognosis in gliomaYing-Shi Yuan0Ying-Shi Yuan1Xin Jin2Lu Chen3Jia-Min Liao4Yang Zhang5Ke-Wei Yu6Wei-Kang Li7Shun-Wang Cao8Xian-Zhang Huang9Xian-Zhang Huang10Chun-Min Kang11Chun-Min Kang12Department of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Neurosurgery, Guangdong 999 Brain Hospital, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaDepartment of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, ChinaBackgroundGlioma 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1027794/fullgliomanecroptosisprognostic modelimmune infiltrationimmune checkpoint
spellingShingle Ying-Shi Yuan
Ying-Shi Yuan
Xin Jin
Lu Chen
Jia-Min Liao
Yang Zhang
Ke-Wei Yu
Wei-Kang Li
Shun-Wang Cao
Xian-Zhang Huang
Xian-Zhang Huang
Chun-Min Kang
Chun-Min Kang
A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma
Frontiers in Immunology
glioma
necroptosis
prognostic model
immune infiltration
immune checkpoint
title A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma
title_full A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma
title_fullStr A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma
title_full_unstemmed A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma
title_short A novel model based on necroptosis-related genes for predicting immune status and prognosis in glioma
title_sort novel model based on necroptosis related genes for predicting immune status and prognosis in glioma
topic glioma
necroptosis
prognostic model
immune infiltration
immune checkpoint
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.1027794/full
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