Research Paper Volume 13, Issue 9 pp 12431—12455
Identification of a mesenchymal-related signature associated with clinical prognosis in glioma
- 1 Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
- 2 Cerebral Vascular Disease Research Center, Anhui Medical University, Hefei 230601, China
Received: November 30, 2020 Accepted: March 4, 2021 Published: April 19, 2021https://doi.org/10.18632/aging.202886
How to Cite
Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Malignant glioma with a mesenchymal (MES) signature is characterized by shorter survival time due to aggressive dissemination and resistance to chemoradiotherapy. Here, this study used the TCGA database as the training set and the CGGA database as the testing set. Consensus clustering was performed on the two data sets, and it was found that two groups had distinguished prognostic and molecular features. Cox analysis and Lasso regression analysis were used to construct MES signature-based risk score model of glioma. Our results show that MES signature-based risk score model can be used to assess the prognosis of glioma. Three methods (ROC curve analyses, univariate Cox regression analysis, multivariate Cox regression analysis) were used to investigate the prognostic role of texture parameters. The result showed that the MES-related gene signature was proved to be an independent prognostic factor for glioma. Furthermore, functional analysis of the gene related to the risk signature showed that the genes sets were closely related to the malignant process of tumors. Finally, FCGR2A and EHD2 were selected for functional verification. Silencing these two genes inhibited the proliferation, migration and invasion of gliomas and reduced the expression of mesenchymal marker genes. Collectively, MES-related risk signature seems to provide a novel target for predicting the prognosis and treatment of glioma.
TCGA: The Cancer Genome Atlas; GTEx: Genotype-Tissue Expression; CGGA: Chinese Glioma Genome Atlas; Ivy GAP: Ivy Glioblastoma Atlas Project; GBM: glioblastoma multiforme; EMT: Epithelial-Mesenchymal Transition; MES: mesenchymal subtype; PN: proneural subtype; Prolif: proliferative subtype; GSEA: Gene set enrichment analysis; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; FCGR2A: Fc fragment of IgG receptor IIa; EHD2: EH Domain Containing 2; CHI3L1: Chitinase 3 Like 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; CD44: CD44 Molecule; SERPINE1: Serpin Family E Member 1; PDPN: Podoplanin; STAT3: signal transducer and activator of transcription 3; C/EBPb: CCAAT Enhancer Binding Protein Beta; TAZ: Tafazzin; EMP3: Epithelial Membrane Protein 3; PLAUR: Plasminogen Activator: Urokinase Receptor; MVP: Major Vault Protein; RRAS: RAS Related; VIM: Vimentin; BMI1: BMI1 Proto-Oncogene: Polycomb Ring Finger; ZEB1: Zinc Finger E-Box Binding Homeobox 1.