Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jun 2:26:e921947.
doi: 10.12659/MSM.921947.

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

Yan Liu  1 , Zhennan Xu  1 , Tao Jin  1 , Ke Xu  1 , Mingfa Liu  1 , Haixiong Xu  1
Affiliations

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

Yan Liu et al. Med Sci Monit. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

None.

Figures

Figure 1
Figure 1
The affinity propagation algorithm of GO and KEGG indicated that the lipoxygenase pathway and carboxylic acid metabolic process (Exemplar) were the critical pathways of 45 proteins.
Figure 2
Figure 2
(A) 5 of 8 genes in the ptimazed panel including ALOX5, CD44, CISD1, FTL, SLC1A5 were significantly associated to the methylation state of MGMT. CISD1 shows a positive correlation (P<0.001) while the other four genes negative (P<0.001). (B) ALOX5, CD44, FTL, NFE2L2, SLCA5 were negative correlated to the tumor purity (P<0.001). (C) The optimazed panel was statistically associated to the 2 key enzymes of methionine cycle, MAT2A and SAHH (P<0.001).
Figure 3
Figure 3
(A) The optimized panel was effective in predicting the OS and PFS of low-grade glioma (P<0.001). It was useless in predicting the OS of glioblastoma but might be potentially used for predicting the PFS of glioblastoma (P=0.017). (B): ALOX5, CD44, FANCD2, NFE2L2, and SLC1A5 were increased in glioma, especially in GBM (P<0.001), while GOT1 was decreased in glioma (P<0.001).
See this image and copyright information in PMC

References

    1. Kierszenbaum AL. Histology and cell biology: An introduction to pathology. 2nd ed. Philadelphia, PA: Mosby Elsevier; 2007.
    1. Vanden Berghe T, Linkermann A, Jouan-Lanhouet ST, et al. Regulated necrosis: the expanding network of non-apoptotic cell death pathways. Nat Rev Mol Cell Biol. 2014;15(2):135–47. - PubMed
    1. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72. - PMC - PubMed
    1. Cookson BT, Brennan MA. Pro-inflammatory programmed cell death. Trends Microbiol. 2001;9(3):113–14. - PubMed
    1. Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171(2):273–85. - PMC - PubMed

MeSH terms