Integrative analysis of metabolism subtypes and identification of prognostic metabolism-related genes for glioblastoma

Author:

Li Jiahui12,Wei Yutian3,Liu Jiali2,Cheng Shupeng2,Zhang Xia4,Qiu Huaide5,Li Jianan2ORCID,He Chuan1

Affiliation:

1. 1Department of Rehabilitation Medicine, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, Jiangsu Province 215228, China

2. 2Center of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province 210029, China

3. 3Neurovascular Center, Changhai Hospital, Naval Medical University, Shanghai, 200433, China

4. 4Center of Rehabilitation Medicine, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi Province 710054, China

5. 5Faculty of Rehabilitation Science, Nanjing Normal University of Special Education, Nanjing, Jiangsu Province 210038, China

Abstract

Abstract Increasing evidence has demonstrated that cancer cell metabolism is a critical factor in tumor development and progression; however, its role in glioblastoma (GBM) remains limited. In the present study, we classified GBM into three metabolism subtypes (MC1, MC2, and MC3) through cluster analysis of 153 GBM samples from the RNA-sequencing data of The Cancer Genome Atlas (TCGA) based on 2752 metabolism-related genes (MRGs). We further explored the prognostic value, metabolic signatures, immune infiltration, and immunotherapy sensitivity of the three metabolism subtypes. Moreover, the metabolism scoring model was established to quantify the different metabolic characteristics of the patients. Results showed that MC3, which is associated with a favorable survival outcome, had higher proportions of isocitrate dehydrogenase (IDH) mutations and lower tumor purity and proliferation. The MC1 subtype, which is associated with the worst prognosis, shows a higher number of segments and homologous recombination defects and significantly lower mRNA expression-based stemness index (mRNAsi) and epigenetic-regulation-based mRNAsi. The MC2 subtype has the highest T-cell exclusion score, indicating a high likelihood of immune escape. The results were validated using an independent dataset. Five MRGs (ACSL1, NDUFA2, CYP1B1, SLC11A1, and COX6B1) correlated with survival outcomes were identified based on metabolism-related co-expression module analysis. Laboratory-based validation tests further showed the expression of these MRGs in GBM tissues and how their expression influences cell function. The results provide a reference for developing clinical management approaches and treatments for GBM.

Funder

the Introduced Project of the Suzhou Clinical Medical Expert Team

the Nanjing Municipal Science and Technology Bureau

the Postgraduate Research & Practice Innovation Program of Jiangsu Province

Publisher

Portland Press Ltd.

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