Development of prognostic indicator based on NAD+ metabolism related genes in glioma
BackgroundStudies have shown that Nicotinamide adenine dinucleotide (NAD+) metabolism can promote the occurrence and development of glioma. However, the specific effects and mechanisms of NAD+ metabolism in glioma are unclear and there were no systematic researches about NAD+ metabolism related gene...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Surgery |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fsurg.2023.1071259/full |
| _version_ | 1797942601471492096 |
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| author | Xiao Chen Xiao Chen Wei Wu Wei Wu Yichang Wang Yichang Wang Beichen Zhang Beichen Zhang Haoyu Zhou Haoyu Zhou Jianyang Xiang Jianyang Xiang Xiaodong Li Xiaodong Li Hai Yu Hai Yu Xiaobin Bai Wanfu Xie Minxue Lian Maode Wang Maode Wang Jia Wang Jia Wang |
| author_facet | Xiao Chen Xiao Chen Wei Wu Wei Wu Yichang Wang Yichang Wang Beichen Zhang Beichen Zhang Haoyu Zhou Haoyu Zhou Jianyang Xiang Jianyang Xiang Xiaodong Li Xiaodong Li Hai Yu Hai Yu Xiaobin Bai Wanfu Xie Minxue Lian Maode Wang Maode Wang Jia Wang Jia Wang |
| author_sort | Xiao Chen |
| collection | DOAJ |
| description | BackgroundStudies have shown that Nicotinamide adenine dinucleotide (NAD+) metabolism can promote the occurrence and development of glioma. However, the specific effects and mechanisms of NAD+ metabolism in glioma are unclear and there were no systematic researches about NAD+ metabolism related genes to predict the survival of patients with glioma.MethodsThe research was performed based on expression data of glioma cases in the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Firstly, TCGA-glioma cases were classified into different subtypes based on 49 NAD+ metabolism-related genes (NMRGs) by consensus clustering. NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were gotten by intersecting the 49 NMRGs and differentially expressed genes (DEGs) between normal and glioma samples. Then a risk model was built by Cox analysis and the least shrinkage and selection operator (LASSO) regression analysis. The validity of the model was verified by survival curves and receiver operating characteristic (ROC) curves. In addition, independent prognostic analysis of the risk model was performed by Cox analysis. Then, we also identified different immune cells, HLA family genes and immune checkpoints between high and low risk groups. Finally, the functions of model genes at single-cell level were also explored.ResultsConsensus clustering classified glioma patients into two subtypes, and the overall survival (OS) of the two subtypes differed. A total of 11 NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were screened by overlapping 5,995 differentially expressed genes (DEGs) and 49 NAD+ metabolism-related genes (NMRGs). Next, four model genes, PARP9, BST1, NMNAT2, and CD38, were obtained by Cox regression and least absolute shrinkage and selection operator (Lasso) regression analyses and to construct a risk model. The OS of high-risk group was lower. And the area under curves (AUCs) of Receiver operating characteristic (ROC) curves were >0.7 at 1, 3, and 5 years. Cox analysis showed that age, grade G3, grade G4, IDH status, ATRX status, BCR status, and risk Scores were reliable independent prognostic factors. In addition, three different immune cells, Mast cells activated, NK cells activated and B cells naive, 24 different HLA family genes, such as HLA-DPA1 and HLA-H, and 8 different immune checkpoints, such as ICOS, LAG3, and CD274, were found between the high and low risk groups. The model genes were significantly relevant with proliferation, cell differentiation, and apoptosis.ConclusionThe four genes, PARP9, BST1, NMNAT2, and CD38, might be important molecular biomarkers and therapeutic targets for glioma patients. |
| first_indexed | 2024-04-10T20:10:03Z |
| format | Article |
| id | doaj.art-514f87421f744c08a789f7cdcc74505c |
| institution | Directory Open Access Journal |
| issn | 2296-875X |
| language | English |
| last_indexed | 2024-04-10T20:10:03Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Surgery |
| spelling | doaj.art-514f87421f744c08a789f7cdcc74505c2023-01-26T11:30:04ZengFrontiers Media S.A.Frontiers in Surgery2296-875X2023-01-011010.3389/fsurg.2023.10712591071259Development of prognostic indicator based on NAD+ metabolism related genes in gliomaXiao Chen0Xiao Chen1Wei Wu2Wei Wu3Yichang Wang4Yichang Wang5Beichen Zhang6Beichen Zhang7Haoyu Zhou8Haoyu Zhou9Jianyang Xiang10Jianyang Xiang11Xiaodong Li12Xiaodong Li13Hai Yu14Hai Yu15Xiaobin Bai16Wanfu Xie17Minxue Lian18Maode Wang19Maode Wang20Jia Wang21Jia Wang22Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaCenter for Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, ChinaBackgroundStudies have shown that Nicotinamide adenine dinucleotide (NAD+) metabolism can promote the occurrence and development of glioma. However, the specific effects and mechanisms of NAD+ metabolism in glioma are unclear and there were no systematic researches about NAD+ metabolism related genes to predict the survival of patients with glioma.MethodsThe research was performed based on expression data of glioma cases in the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Firstly, TCGA-glioma cases were classified into different subtypes based on 49 NAD+ metabolism-related genes (NMRGs) by consensus clustering. NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were gotten by intersecting the 49 NMRGs and differentially expressed genes (DEGs) between normal and glioma samples. Then a risk model was built by Cox analysis and the least shrinkage and selection operator (LASSO) regression analysis. The validity of the model was verified by survival curves and receiver operating characteristic (ROC) curves. In addition, independent prognostic analysis of the risk model was performed by Cox analysis. Then, we also identified different immune cells, HLA family genes and immune checkpoints between high and low risk groups. Finally, the functions of model genes at single-cell level were also explored.ResultsConsensus clustering classified glioma patients into two subtypes, and the overall survival (OS) of the two subtypes differed. A total of 11 NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were screened by overlapping 5,995 differentially expressed genes (DEGs) and 49 NAD+ metabolism-related genes (NMRGs). Next, four model genes, PARP9, BST1, NMNAT2, and CD38, were obtained by Cox regression and least absolute shrinkage and selection operator (Lasso) regression analyses and to construct a risk model. The OS of high-risk group was lower. And the area under curves (AUCs) of Receiver operating characteristic (ROC) curves were >0.7 at 1, 3, and 5 years. Cox analysis showed that age, grade G3, grade G4, IDH status, ATRX status, BCR status, and risk Scores were reliable independent prognostic factors. In addition, three different immune cells, Mast cells activated, NK cells activated and B cells naive, 24 different HLA family genes, such as HLA-DPA1 and HLA-H, and 8 different immune checkpoints, such as ICOS, LAG3, and CD274, were found between the high and low risk groups. The model genes were significantly relevant with proliferation, cell differentiation, and apoptosis.ConclusionThe four genes, PARP9, BST1, NMNAT2, and CD38, might be important molecular biomarkers and therapeutic targets for glioma patients.https://www.frontiersin.org/articles/10.3389/fsurg.2023.1071259/fullgliomanicotinamide adenine dinucleotidePARP9BST1NMNAT2CD38 |
| spellingShingle | Xiao Chen Xiao Chen Wei Wu Wei Wu Yichang Wang Yichang Wang Beichen Zhang Beichen Zhang Haoyu Zhou Haoyu Zhou Jianyang Xiang Jianyang Xiang Xiaodong Li Xiaodong Li Hai Yu Hai Yu Xiaobin Bai Wanfu Xie Minxue Lian Maode Wang Maode Wang Jia Wang Jia Wang Development of prognostic indicator based on NAD+ metabolism related genes in glioma Frontiers in Surgery glioma nicotinamide adenine dinucleotide PARP9 BST1 NMNAT2 CD38 |
| title | Development of prognostic indicator based on NAD+ metabolism related genes in glioma |
| title_full | Development of prognostic indicator based on NAD+ metabolism related genes in glioma |
| title_fullStr | Development of prognostic indicator based on NAD+ metabolism related genes in glioma |
| title_full_unstemmed | Development of prognostic indicator based on NAD+ metabolism related genes in glioma |
| title_short | Development of prognostic indicator based on NAD+ metabolism related genes in glioma |
| title_sort | development of prognostic indicator based on nad metabolism related genes in glioma |
| topic | glioma nicotinamide adenine dinucleotide PARP9 BST1 NMNAT2 CD38 |
| url | https://www.frontiersin.org/articles/10.3389/fsurg.2023.1071259/full |
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