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Exploring the multidimensional heterogeneities of glioblastoma multiforme based on sample-specific edge perturbation in gene interaction network

Authors :
Jianglin Zheng
Yue Qiu
Zhipeng Wu
Xuan Wang
Xiaobing Jiang
Source :
Frontiers in Immunology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Glioblastoma multiforme (GBM) is the most malignant brain cancer with great heterogeneities in many aspects, such as prognosis, clinicopathological features, immune landscapes, and immunotherapeutic responses. Considering that gene interaction network is relatively stable in a healthy state but widely perturbed in cancers, we sought to explore the multidimensional heterogeneities of GBM through evaluating the degree of network perturbations. The gene interaction network perturbations of GBM samples (TCGA cohort) and normal samples (GTEx database) were characterized by edge perturbations, which were quantized through evaluating the change in relative gene expression value. An unsupervised consensus clustering analysis was performed to identify edge perturbation-based clusters of GBM samples. Results revealed that the edge perturbation of GBM samples was stronger than that of normal samples. Four edge perturbation-based clusters of GBM samples were identified and showed prominent heterogeneities in prognosis, clinicopathological features, somatic genomic alterations, immune landscapes, and immunotherapeutic responses. In addition, a sample-specific perturbation of gene interaction score (SPGIScore) was constructed based on the differently expressed genes (DEGs) among four clusters, and exhibited a robust ability to predict prognosis. In conclusion, the bioinformatics approach based on sample-specific edge perturbation in gene interaction network provided a new perspective to understanding the multidimensional heterogeneities of GBM.

Details

Language :
English
ISSN :
16643224
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.7a007281f7684835ab04d03df848a2aa
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2022.944030