PDF(Pubmed)
Abstract：
The Ten-Eleven Translocation (TET) family genes are implicated in a wide array of biological functions across various human cancers. Nonetheless, there is a scarcity of studies that comprehensively analyze the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Leveraging updated public databases and employing several bioinformatics analysis methods, we assessed the expression levels, somatic variations, methylation levels, and prognostic values of TET family genes. Additionally, we explored the association between the expression of TET family genes and pathway activity, tumor microenvironment (TME), stemness score, immune subtype, clinical staging, and drug sensitivity in pan-cancer. Molecular biology and cytology experiments were conducted to validate the potential role of TET3 in tumor progression. Each TET family gene displayed distinct expression patterns across at least ten detected tumors. The frequency of Single Nucleotide Variant (SNV) in TET genes was found to be 91.24%, primarily comprising missense mutation types, with the main types of copy number variant (CNV) being heterozygous amplifications and deletions. TET1 gene exhibited high methylation levels, whereas TET2 and TET3 genes displayed hypomethylation in most cancers, which correlated closely with patient prognosis. Pathway activity analysis revealed the involvement of TET family genes in multiple signaling pathways, including cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. Furthermore, the expression levels of TET family genes were shown to impact the clinical staging of tumor patients, modulate the sensitivity of chemotherapy drugs, and thereby influence patient prognosis by participating in the regulation of the tumor microenvironment, cellular stemness potential, and immune subtype. Notably, TET3 was identified to promote cancer progression across various tumors, and its silencing was found to inhibit tumor malignancy and enhance chemotherapy sensitivity. These findings shed light on the role of TET family genes in cancer progression and offer insights for further research on TET3 as a potential therapeutic target for pan-cancer.
摘要：
10-11易位(TET)家族基因涉及各种人类癌症的广泛生物学功能。尽管如此，缺乏全面分析TET家族成员与不同癌症分子表型和临床特征相关性的研究。利用更新的公共数据库，并采用几种生物信息学分析方法，我们评估了表达水平，体细胞变异，甲基化水平，和TET家族基因的预后价值。此外,我们探索了TET家族基因的表达与通路活性之间的关联，肿瘤微环境（TME），干性得分，免疫亚型，临床分期,和泛癌症的药物敏感性。进行分子生物学和细胞学实验以验证TET3在肿瘤进展中的潜在作用。每个TET家族基因在至少十个检测到的肿瘤中显示出不同的表达模式。发现TET基因中单核苷酸变异(SNV)的频率为91.24%,主要包括错义突变类型，拷贝数变体(CNV)的主要类型是杂合扩增和缺失。TET1基因表现出高甲基化水平，而TET2和TET3基因在大多数癌症中表现出低甲基化，与患者预后密切相关。通路活性分析显示TET家族基因参与多个信号通路,包括细胞周期，凋亡，DNA损伤反应,激素AR，PI3K/AKT,RTK。此外，TET家族基因的表达水平对肿瘤患者的临床分期有影响,调节化疗药物的敏感性，从而通过参与肿瘤微环境的调节来影响患者的预后，细胞干细胞潜能，和免疫亚型。值得注意的是,TET3被确定为促进各种肿瘤的癌症进展，发现其沉默可以抑制肿瘤的恶性程度并增强化疗敏感性。这些发现揭示了TET家族基因在癌症进展中的作用，并为进一步研究TET3作为泛癌症的潜在治疗靶标提供了见解。
