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

Author:

Zeng Wen-Jing12,Cao Yu-Fang3,Li He4,Gong Zhi-Cheng12,Wu Wantao25,Luo Peng6ORCID,Zhang Jian6,Liu Zaoqu7ORCID,Zhang Hao28ORCID,Cheng Quan28ORCID

Affiliation:

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

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

3. Department of Pharmacy, Hunan University of Medicine, Huaihua, Hunan, China

4. Hunan Clinical Research Center in Gynecologic Cancer, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China

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

6. Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China

7. Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou, Zhengzhou, Henan, China

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

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 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.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Oncology

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