The Seventh Department of General Surgery, The First Hospital of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China.
Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, No.88, Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Biochem Genet. 2024 Apr;62(2):718-740. doi: 10.1007/s10528-023-10442-5. Epub 2023 Jul 6.
To investigate the function of ten-eleven translocation 1 (TET1) and its underlying mechanism in papillary thyroid cancer (PTC). Using the RNA-Seq data based on GDC TCGA, we analyzed the gene expression pattern of TET1 in PTC. Immunohistochemistry was carried out to assess the TET1 protein level. Then, its diagnostic and prognostic functions were determined by various bioinformatics approaches. Enrichment analysis was performed to explore the potential pathways in which TET1 is mainly involved. Finally, the immune cell infiltration analysis was conducted and the association of TET1 mRNA expression with the expression levels of immune checkpoints, tumor mutation burden (TMB) score, microsatellite instability (MSI) score, and cancer stem cells (CSC) score was examined. TET1 expression was lower in PTC tissues compared with that in normal tissues (P < 0.01). Besides, TET1 had a certain value in diagnosing PTC, and low-TET1 mRNA expression led to favorable disease-specific survival (DSS) (P < 0.01). The enrichment analysis revealed autoimmune thyroid disease and cytokine-cytokine receptor interaction were the consistent pathways in which TET1 participated. TET1 was negatively correlated with the Stromal score and Immune score. The different proportions of immune cell subtypes were observed between high- and low-TET1 expression groups. Interestingly, TET1 mRNA expression was inversely related to the expression levels of immune checkpoints, and TMB, MSI, and CSC scores. TET1 might be a robust diagnostic and prognostic biomarker for PTC. TET1 affected the DSS of PTC patients possibly through the regulation of immune-related pathways and tumor immunity.
为了研究十号十一号转位酶 1(TET1)在甲状腺乳头状癌(PTC)中的功能及其潜在机制。我们使用基于 GDC TCGA 的 RNA-Seq 数据,分析了 TET1 在 PTC 中的基因表达模式。通过免疫组织化学评估 TET1 蛋白水平。然后,通过各种生物信息学方法确定其诊断和预后功能。进行富集分析以探索 TET1 主要参与的潜在途径。最后,进行免疫细胞浸润分析,并检查 TET1 mRNA 表达与免疫检查点、肿瘤突变负担(TMB)评分、微卫星不稳定性(MSI)评分和癌症干细胞(CSC)评分的表达水平之间的关联。与正常组织相比,PTC 组织中 TET1 的表达较低(P<0.01)。此外,TET1 在诊断 PTC 方面具有一定的价值,低 TET1 mRNA 表达导致良好的疾病特异性生存(DSS)(P<0.01)。富集分析表明自身免疫性甲状腺疾病和细胞因子-细胞因子受体相互作用是 TET1 参与的一致途径。TET1 与基质评分和免疫评分呈负相关。在高表达和低表达 TET1 的组之间观察到不同比例的免疫细胞亚型。有趣的是,TET1 mRNA 表达与免疫检查点、TMB、MSI 和 CSC 评分的表达水平呈负相关。TET1 可能是 PTC 的一种强大的诊断和预后生物标志物。TET1 通过调节免疫相关途径和肿瘤免疫可能影响 PTC 患者的 DSS。