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- Title
Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme.
- Authors
Han, Xudong; Wang, Donghua; Zhao, Ping; Liu, Chonghui; Hao, Yue; Chang, Lulu; Zhao, Jiarui; Zhao, Wei; Mu, Lili; Wang, Jinghua; Li, Hulun; Kong, Qingfei; Han, Junwei
- Abstract
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most malignant form of glioma and represents 81% of malignant brain and central nervous system (CNS) tumors. Like most cancers, GBM causes metabolic recombination to promote cell survival, proliferation, and invasion of cancer cells. In this study, we propose a method for constructing the metabolic subpathway activity score matrix to accurately identify abnormal targets of GBM metabolism. By integrating gene expression data from different sequencing methods, our method identified 25 metabolic subpathways that were significantly abnormal in the GBM patient population, and most of these subpathways have been reported to have an effect on GBM. Through the analysis of 25 GBM-related metabolic subpathways, we found that (S)-2,3-Epoxysqualene, which was at the central region of the sterol biosynthesis subpathway, may have a greater impact on the entire pathway, suggesting a potential high association with GBM. Analysis of CCK8 cell activity indicated that (S)-2,3-Epoxysqualene can indeed inhibit the activity of U87-MG cells. By flow cytometry, we demonstrated that (S)-2,3-Epoxysqualene not only arrested the U87-MG cell cycle in the G0/G1 phase but also induced cell apoptosis. These results confirm the reliability of our proposed metabolic subpathway identification method and suggest that (S)-2,3-Epoxysqualene has potential therapeutic value for GBM. In order to make the method more broadly applicable, we have developed an R system package crmSubpathway to perform disease-related metabolic subpathway identification and it is freely available on the GitHub (https://github.com/hanjunwei-lab/crmSubpathway).
- Subjects
GLIOBLASTOMA multiforme; GLIOMAS; CENTRAL nervous system tumors; OLIGODENDROGLIOMAS; CENTRAL nervous system; CANCER cells; CELL analysis
- Publication
Frontiers in Oncology, 2020, Vol 10, pN.PAG
- ISSN
2234-943X
- Publication type
Article
- DOI
10.3389/fonc.2020.01549