In:
Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-4-28)
Abstract:
Glioblastoma multiforme (GBM) is the most common type of malignant brain tumor, among which IDH1-wild type GBM has a poor prognosis. Recent studies have shown that ferroptosis-related genes (FRGs) are correlated with the development and progression of cancer. In GBM, the role of FRGs associated with IDH1 status as biological indicators and therapeutic targets remains to be clarified. Ten of FRGs (STEAP3, HSPB1, MAP1LC3A, SOCS1, LOX, CAPG, CP, GDF15, CDKN1A, and CD44) associated with IDH1 status in GBM were identified as key genes through screening by survival analysis and Random Forest using The Cancer Genome Atlas (TCGA) datasets, and the protein expressions of key genes were verified. Transwell and qPCR results showed that ferroptosis promoted the migration of glioblastoma cells and affected the expression of key genes. Our study established the ferroptosis-related prognostic model for GBM patients based on ten key genes by a different modeling method from previous study, the GSVA algorithm. Further, we took the methods of functional enrichment analysis, clinical characteristics, immune cell infiltration, immunomodulator, ESTIMATE and single nucleotide variant (SNV) analysis to study the molecular mechanisms of prognostic model and key genes. The results showed that ten key genes were strongly associated with immune-related factors and were significantly involved in the p53 signaling pathway, senescence and autophagy in cancer, and in the negative regulation of protein kinase activity. Moreover, potential therapeutic drugs were identified by Virtual Screening and Molecular Docking. Our study indicated that the novel ferrotosis-related prognostic model for GBM patients and key genes possessed the prognostic and therapeutic values.
Type of Medium:
Online Resource
ISSN:
1663-9812
DOI:
10.3389/fphar.2022.898679
DOI:
10.3389/fphar.2022.898679.s001
DOI:
10.3389/fphar.2022.898679.s002
DOI:
10.3389/fphar.2022.898679.s003
DOI:
10.3389/fphar.2022.898679.s004
DOI:
10.3389/fphar.2022.898679.s005
DOI:
10.3389/fphar.2022.898679.s006
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2587355-6
SSG:
15,3
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