Clinical And Biological Significances Of Ferroptosis-Related Gene GCLC In Glioblastoma

Objective:Ferroptosis is an iron-dependent cell death.Ferroptosis-related genes(FRGs)have been shown to be involved in the occurrence and development of various tumors and are potential targets for tumor treatment.Ferroptosis-related genes glutamate-cysteine The role of the catalytic subunit of amino acid ligase(GCLC)in glioblastoma remains to be studied,and this study aims to investigate the clinical and biological significance of GCLC in glioblastoma(GBM).Methods:The expression of glutamate-cysteine ligase catalytic subunit(GCLC)was detected by The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO)and immunohistochemistry,and the relationship between GCLC and patients’ clinical parameters and lymphocytes was analyzed.A protein network interacting with GCLC was constructed through the STRING database.Linked Omics database was used to screen the co-expressed genes of GCLC and perform enrichment analysis.The relationship between GCLC and tumor immunity was analyzed using TISIDB database.Results:We found that GCLC was overexpressed in most tumors including glioma,and the expression of GCLC m RNA was significantly higher in GBM samples than in non-tumor brain tissue samples.The expression level of GCLC was significantly correlated with WHO grade,IDH status,1p/19 q co-deletion and age.Immunohistochemistry revealed that GCLC protein levels were higher in GBM tissues than in normal tissues.GO-BP(Geneontologybiologicalprocess)and KEGG(Kyoto Encyclopediaof Genesand Genomes)enrichment analysis found that ion transport,amino acid and fatty acid metabolism,and ferroptosis were significantly enriched.We also found that the expression of GCLC in glioblastoma(GBM)was significantly correlated with several tumor-infiltrating lymphocytes and immune-related markers.Conclusion:Our study found that the expression of GCLC was significantly upregulated in GBM and correlated with clinical parameters in glioma patients.Overexpression of GCLC can affect the abundance of tumor-infiltrating lymphocytes and immune-related factors.The regulation of GCLC expression may be a new perspective to induce ferroptosis in the treatment of glioblastoma.