Ferroptosis in Low-Grade Glioma: A New Marker for Diagnosis and Prognosis

BACKGROUND The extent of glioma resection influences the overall survival (OS) and progression-free survival (PFS). Ferroptosis is a newly recognized type of cell death, which may be associated with low-grade glioma border detection and OS. This study is assessed an optimized ferroptosis gene panel for glioma treatment. MATERIAL AND METHODS We obtained 45 reports on ferroptosis-related proteins in PubMed and conducted a statistical test of the patients' overall survival (OS) in the TCGA GBMLGG and CGGA databases. The statistically significant genes were screened for an optimal panel, followed by GO and KEGG analysis and evaluated its correlation with known prognostic factors of glioma, including IDH1 mutation, methylated MGMT, tumor purity, 1p/19q LOH, and methionine cycle. RESULTS Eight genes panel (ALOX5, CISD1, FTL, CD44, FANCD2, NFE2L2, SLC1A5, and GOT1) were highly related to OS (P<0.001) and PFS (P<0.001) of low-grade glioma (LGG) patients, out of which 6 genes (ALOX5, CISD1, CD44, FTL, FANCD2, and SLC1A5) were correlated with IDH1_p.R132H (P<0.001) and 5 genes (ALOX5, CD44, FTL, NFE2L2, SLC1A5) showed a correlation with tumor purity (P<0.001). Five genes (ALOX5, CD44, CISD1, FTL, and SLC1A5) were associated with methylated MGMT (P<0.001), out of which 6 genes (ALOX5, CD44, FANCD2, NFE2L2, SLC1A5, and GOT1) had significantly different expression in healthy brain tissue vs. glioma (P<0.001). CONCLUSIONS Our panel of 8 ferroptosis genes showed a significant correlation with the diagnostic and prognostic factors of low-grade glioma and can be applied in neuroradiology and surgery.