Development of a novel glycolysis-related genes signature for isocitrate dehydrogenase 1-associated glioblastoma multiforme.
Development of a novel glycolysis-related genes signature for isocitrate dehydrogenase 1-associated glioblastoma multiforme.
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异柠檬酸脱氢酶 1 相关多形性胶质母细胞瘤的新型糖酵解相关基因特征的开发
DOI：
10.3389/fimmu.2022.950917
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发表时间：
2022
影响因子：
7.3
通讯作者：
Chen, Ming
中科院分区：
文献类型：
--
作者：
Cai, Xiaomin;Chen, Zheng;Huang, Caiquan;Shen, Jie;Zeng, Wenxian;Feng, Shuang;Liu, Yu;Li, Shiting;Chen, Ming
IDH 1野生型和IDH 1突变型多形性胶质母细胞瘤（GBM）预后的显著差异可能归因于它们的代谢差异。因此，我们试图构建一个基于糖酵解相关基因（GRG）的IDH 1相关GBM的预后信号，并进一步研究其与免疫的关系。方法基于TCGA数据库和分子特征数据库（MSigDB），筛选IDH 1野生型和IDH 1突变型GBM差异表达的GRG。使用Consensus Cluster Plus分析和KEGG通路分析来建立新的GRG集。然后进行WGCNA、单变量考克斯和LASSO回归分析以构建预后特征。然后，我们评估了预后标记与患者生存期、临床特征、肿瘤免疫原性、免疫浸润的关联，并验证了一个枢纽基因。结果筛选出956个IDH 1野生型和突变型GBM间差异表达基因（DEG），并筛选出6个关键的与IDH 1突变型GBM相关的基因，构建了IDH 1突变型GBM的预后标记。进一步的评估和验证表明，签名独立预测GBM患者的预后，具有中等的准确性。此外，预后特征还与临床特征（性别和MGMT启动子状态）、肿瘤免疫原性（mRNAsi、EREG-mRNAsi和HRD-TAI）和免疫浸润（干性指数、免疫细胞浸润、免疫评分和基因突变）显著相关。在六个关键的肿瘤相关GRG中，CLEC 5A被选择并验证为在GBM中潜在地发挥致癌作用。结论构建GRGs预后信号并鉴定其与免疫景观的密切相关性，为GBM的免疫治疗提供了潜在的应用前景。
Background The significant difference in prognosis between IDH1 wild-type and IDH1 mutant glioblastoma multiforme (GBM) may be attributed to their metabolic discrepancies. Hence, we try to construct a prognostic signature based on glycolysis-related genes (GRGs) for IDH1-associated GBM and further investigate its relationships with immunity. Methods Differentially expressed GRGs between IDH1 wild-type and IDH1 mutant GBM were screened based on the TCGA database and the Molecular Signature Database (MSigDB). Consensus Cluster Plus analysis and KEGG pathway analyses were used to establish a new GRGs set. WGCNA, univariate Cox, and LASSO regression analyses were then performed to construct the prognostic signature. Then, we evaluated association of the prognostic signature with patients’ survival, clinical characteristics, tumor immunogenicity, immune infiltration, and validated one hub gene. Results 956 differentially expressed genes (DEGs) between IDH1 wild-type and mutant GBM were screened out and six key prognostically related GRGs were rigorously selected to construct a prognostic signature. Further evaluation and validation showed that the signature independently predicted GBM patients’ prognosis with moderate accuracy. In addition, the prognostic signature was also significantly correlated with clinical traits (sex and MGMT promoter status), tumor immunogenicity (mRNAsi, EREG-mRNAsi and HRD-TAI), and immune infiltration (stemness index, immune cells infiltration, immune score, and gene mutation). Among six key prognostically related GRGs, CLEC5A was selected and validated to potentially play oncogenic roles in GBM. Conclusion Construction of GRGs prognostic signature and identification of close correlation between the signature and immune landscape would suggest its potential applicability in immunotherapy of GBM in the future.
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肿瘤基因对神经元和星形胶质细胞的去分化会在小鼠中诱导神经胶质瘤。
DOI：
10.1126/science.1226929
发表时间：
2012-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Friedmann-Morvinski D;Bushong EA;Ke E;Soda Y;Marumoto T;Singer O;Ellisman MH;Verma IM
通讯作者：
Verma IM
DOI：
10.1016/j.urolonc.2018.12.009
发表时间：
2019-04-01
影响因子：
2.7
作者：
Chan, Ti-Chun;Li, Chien-Feng;Li, Wei-Ming
通讯作者：
Li, Wei-Ming
影响因子：
6.6
作者：
Ježek P
通讯作者：
Ježek P
影响因子：
3.8
作者：
Ngoh A;McTague A;Wentzensen IM;Meyer E;Applegate C;Kossoff EH;Batista DA;Wang T;Kurian MA
通讯作者：
Kurian MA
影响因子：
5
作者：
Cai J;Gao L;Wang Y;Li Y;Ye Z;Tong S;Yan T;Sun Q;Xu Y;Jiang H;Zhang S;Zhao L;Yang J;Chen Q
通讯作者：
Chen Q