A Novel Thrombosis-Related Signature for Predicting Survival and Drug Compounds in Glioblastoma.
A Novel Thrombosis-Related Signature for Predicting Survival and Drug Compounds in Glioblastoma.
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用于预测胶质母细胞瘤生存和药物化合物的新型血栓相关特征
作者：
胶质母细胞瘤是中枢神经系统最常见的原发性肿瘤，血栓形成相关基因与其发生、发展有关。单变量考克斯和LASSO回归分析用于开发基于血栓形成相关基因的新预后标记。基因本体（GO），京都基因和基因组百科全书（KEGG），和HALLMARK用于风险签名的功能注释。使用ESTIMATE、MCP-计数器、xCell和TIMER算法定量肿瘤微环境中的免疫浸润。癌症药物敏感性基因组学（GDSC）用于选择潜在的药物化合物。基于血栓形成相关基因的风险特征在预后预测中表现中等。风险特征的功能注释表明，与细胞周期、凋亡、肿瘤发生和免疫抑制相关的信号通路在高危组中丰富。体细胞突变分析显示，抑癌基因TP 53和癌基因PTEN分别在低危组和高危组中有较高的表达。在风险评分组中探索潜在的药物化合物，并且在低风险评分组中显示出较高的AUC值。具有有价值的预后因素的诺模图在预测GBM患者的生存结局方面具有高灵敏度。我们的研究筛选出了GBM中具有显著临床意义的多个血栓相关基因，并进一步开发了一种有意义的预测药物敏感性和生存结局的预后风险特征。
Glioblastoma is the most common primary tumor in the central nervous system, and thrombosis-associated genes are related to its occurrence and progression. Univariate Cox and LASSO regression analysis were utilized to develop a new prognostic signature based on thrombosis-associated genes. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and HALLMARK were used for functional annotation of risk signature. ESTIMATE, MCP-counter, xCell, and TIMER algorithms were used to quantify immune infiltration in the tumor microenvironment. Genomics of Drug Sensitivity in Cancer (GDSC) was used for selecting potential drug compounds. Risk signature based on thrombosis-associated genes shows moderate performance in prognosis prediction. The functional annotation of the risk signature indicates that the signaling pathways related to the cell cycle, apoptosis, tumorigenesis, and immune suppression are rich in the high-risk group. Somatic mutation analysis shows that tumor-suppressive gene TP53 and oncogene PTEN have higher expression in low-risk and high-risk groups, respectively. Potential drug compounds are explored in risk score groups and show higher AUC values in the low-risk score group. A nomogram with valuable prognostic factors exhibits high sensitivity in predicting the survival outcome of GBM patients. Our research screens out multiple thromboses-associated genes with remarkable clinical significance in GBM and further develops a meaningful prognostic risk signature predicting drug sensitivity and survival outcome.
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国际神经病理学协会 - 哈勒姆神经系统肿瘤分类和分级共识指南。
DOI：
10.1111/bpa.12171
发表时间：
2014-09
期刊：
Brain pathology (Zurich, Switzerland)
影响因子：
--
作者：
Louis DN;Perry A;Burger P;Ellison DW;Reifenberger G;von Deimling A;Aldape K;Brat D;Collins VP;Eberhart C;Figarella-Branger D;Fuller GN;Giangaspero F;Giannini C;Hawkins C;Kleihues P;Korshunov A;Kros JM;Beatriz Lopes M;Ng HK;Ohgaki H;Paulus W;Pietsch T;Rosenblum M;Rushing E;Soylemezoglu F;Wiestler O;Wesseling P;International Society Of Neuropathology--Haarlem
通讯作者：
International Society Of Neuropathology--Haarlem
影响因子：
168.9
作者：
Ricard, Damien;Idbaih, Ahmed;Delattre, Jean-Yves
通讯作者：
Delattre, Jean-Yves
影响因子：
17.1
作者：
Nunez, Felipe J.;Mendez, Flor M.;Castro, Maria G.
通讯作者：
Castro, Maria G.
DOI：
10.12659/msm.910180
发表时间：
2018-08-16
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Bian A;Wang Y;Liu J;Wang X;Liu D;Jiang J;Ding L;Hui X
通讯作者：
Hui X
影响因子：
5.8
作者：
Ebert LM;Yu W;Gargett T;Toubia J;Kollis PM;Tea MN;Ebert BW;Bardy C;van den Hurk M;Bonder CS;Manavis J;Ensbey KS;Oksdath Mansilla M;Scheer KG;Perrin SL;Ormsby RJ;Poonnoose S;Koszyca B;Pitson SM;Day BW;Gomez GA;Brown MP
通讯作者：
Brown MP