Background
The ten-eleven translocation (TET) protein family, which includes TET1, TET2, and TET3, plays a crucial role in tumorigenesis by either activating or repressing the transcription of target genes in different cellular processes. However, the role of TET protein family in glioma is currently unclear.
Methods
We analyzed the expression level of TET protein family in pan-cancer and their correlation with prognosis using the GTEx and TCGA databases. We also acquired both genomic sequencing profiles and patients’ clinical details for healthy brain samples and glioma specimens from the databases of TCGA and CGGA. The differential expression of TET protein family in glioma and their correlation with prognosis were analyzed. The results have been subsequently confirmed using immunohistochemistry techniques. To evaluate risk elements associated with the occurrence and progression of glioma, we employed both univariate and multivariate Cox regression analyses. Furthermore, we performed analyses of functional enrichment, specifically focusing on genes related to TET1, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). To evaluate the correlation between immune cell infiltration level and TET1 expression in glioma, we employed the single-sample GSEA (ssGSEA) approach. Moreover, we investigated the association between TET1 and drug sensitivity.
Results
Expression levels of TET protein family were markedly increased in glioma relative to normal tissue. The increase is more significant in IDH-mutant glioma compared to IDH-wildtype glioma, as confirmed by immunohistochemical analysis. TET1 expression levels correlate with tumor grades in glioma, regardless of IDH mutation status, but TET2 and TET3 expressions do not show a similar relationship. TET1 was also found to be an independent prognostic factor for glioma by univariate and multifactorial Cox analysis. Research on biological processes has revealed a strong correlation between TET1 and immunity. Additionally, the expression of TET1 showed a correlation with the presence of macrophages, neutrophils, eosinophils, T cells, and Tcm in tumor infiltration. Further study also revealed that TET1 is linked to drug sensitivity.
Conclusion
TET1, rather than TET2 and TET3, is a critical prognostic biomarker that is associated with the progression, prognosis, and immunity in glioma.