Pan-cancer analyses reveal molecular and clinical characteristics of TET family members and suggests that TET3 maybe a potential therapeutic target

Abstract

ABSTRACTThe ten eleven translation (TET) family genes involve a wide range of biological functions in human cancers. However, few studies have comprehensively analyzed the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Based on updated public databases and integrated several bioinformatics analysis methods, we evaluated expression level, somatic variation, methylation level, prognostic values of TET family gene and explore the association between expression of TET family genes and pathway activity, TME, stemness score, immune subtype, clinical staging, drug sensitivity in pan-cancer. Molecular biology and cytology experiments were used to validate the potential role of TET3 in tumor progression. Each TET family gene exhibits differentiated expression in at least ten detected tumors. The frequency of single nucleotide variation (SNV) of TETs gene was 91.24%, with most missense mutation type, and the main types of copy number variation (CNV) are heterozygous amplification and deletion. The TET1 gene is highly methylated, while the TET2 and TET3 genes are hypomethylated in most cancers, and that closely related to patient prognosis. Pathway activity analysis shows that the TET family genes are involved in multiple signaling pathways such as cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. In addition, the expression level of TET family genes also affects the clinical stage of tumor patients, increases or inhibits the sensitivity of chemotherapy drugs, and then affects the prognosis of patients by participating in the regulation of tumor microenvironment (TME), cellular stemness potential, and the immune subtype. It is particularly pointed out that TET3 plays a role in promoting cancer progression in various tumors, and silencing TET3 can inhibit tumor malignancy and increase chemotherapy sensitivity. These findings may elucidate the role of TET family genes in cancer progression and provide insights for further research on TET3 as a potential target for pan-cancer.