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一种用于预测胶质母细胞瘤生存和药物化合物的新型血栓形成相关特征。

A Novel Thrombosis-Related Signature for Predicting Survival and Drug Compounds in Glioblastoma.

作者信息

Zeng Wen-Jing, Cao Yu-Fang, Li He, Gong Zhi-Cheng, Wu Wantao, Luo Peng, Zhang Jian, Liu Zaoqu, Zhang Hao, Cheng Quan

机构信息

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

J Oncol. 2022 Jul 13;2022:6792850. doi: 10.1155/2022/6792850. eCollection 2022.

DOI:10.1155/2022/6792850
PMID:35874629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9300384/
Abstract

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 and oncogene 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.

摘要

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和进展相关。利用单因素Cox和LASSO回归分析,基于血栓形成相关基因开发了一种新的预后特征。基因本体论(GO)、京都基因与基因组百科全书(KEGG)和HALLMARK用于风险特征的功能注释。使用ESTIMATE、MCP-counter、xCell和TIMER算法对肿瘤微环境中的免疫浸润进行量化。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出中等性能。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富集。体细胞突变分析表明,肿瘤抑制基因和癌基因分别在低危组和高危组中具有较高的表达。在风险评分组中探索了潜在的药物化合物,并且在低风险评分组中显示出更高的AUC值。具有有价值预后因素的列线图在预测GBM患者的生存结果方面具有高敏感性。我们的研究筛选出了多个在GBM中具有显著临床意义的血栓形成相关基因,并进一步开发了一个有意义的预后风险特征,用于预测药物敏感性和生存结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc73/9300384/437f2a33d487/JO2022-6792850.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc73/9300384/e4e09ccc07bf/JO2022-6792850.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc73/9300384/2259e25af1c1/JO2022-6792850.004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc73/9300384/437f2a33d487/JO2022-6792850.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc73/9300384/e4e09ccc07bf/JO2022-6792850.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc73/9300384/6c6653abd1bf/JO2022-6792850.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc73/9300384/8bf4c2f65bd6/JO2022-6792850.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc73/9300384/437f2a33d487/JO2022-6792850.007.jpg

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