Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
Department of Hepatobiliary Surgery, Affiliated Huadu Hospital, Southern Medical University (People's Hospital of Huadu District), Guangzhou 510000, China.
Mediators Inflamm. 2023 May 4;2023:2664370. doi: 10.1155/2023/2664370. eCollection 2023.
DNA methylation patterns have been found to be distinct between tumor and normal patients. However, the effect of DNA demethylation enzymes, ten eleven translocation (TET) proteins, has not been comprehensively characterized in liver cancer. In this research, we sought to unravel the linkage of TET proteins with prognosis, immune characteristics and biological pathways in hepatocellular carcinoma (HCC).
Four independent datasets with gene expression data and clinical data of HCC samples were downloaded from public databases. CIBERSORT, single sample Gene Set Enrichment Analysis (ssGSEA), MCP-counter, and TIMER were implemented to evaluate immune cell infiltration. limma was employed to screen differentially expressed genes (DEGs) between two groups. The demethylation-related risk model was established by using univariate Cox regression analysis, the least absolute shrinkage and selection operator (LASSO), and stepwise Akaike information criterion (stepAIC).
TET1 was significantly higher expressed in tumor samples than that in normal samples. HCC patients with advanced stages (III+IV) and grades (G3+G4) had higher TET1 expression compared to early stages (I+II) and grades (G1+G2). HCC samples with high TET1 expression had worse prognosis than that with low expression. High and low TET1 expression groups had distinct immune cell infiltration and response to immunotherapy and chemotherapy. We identified 90 DEGs related to DNA demethylation in high vs. low TET1 expression groups. Furthermore, we established a risk model based on 90 DEGs containing seven key prognostic genes (SERPINH1, CDC20, HACD2, SPHK1, UGT2B15, SLC1A5, and CYP2C9) with effectiveness and robustness in predicting HCC prognosis.
Our study suggested TET1 as a potential indicator in HCC progression. TET1 was closely involved in immune infiltration and activation of oncogenic pathways. The DNA demethylation-related risk model was potential to be applied for predicting HCC prognosis in clinics.
已发现肿瘤患者和正常患者的 DNA 甲基化模式存在明显差异。然而，在肝癌中，尚未全面描述 DNA 去甲基化酶（TET）蛋白的作用。在这项研究中，我们试图揭示 TET 蛋白与肝细胞癌（HCC）预后、免疫特征和生物学途径的联系。
从公共数据库中下载了包含 HCC 样本基因表达数据和临床数据的四个独立数据集。使用 CIBERSORT、单样本基因集富集分析（ssGSEA）、MCP-counter 和 TIMER 评估免疫细胞浸润。使用 limma 筛选两组间差异表达基因（DEGs）。使用单变量 Cox 回归分析、最小绝对值收缩和选择算子（LASSO）和逐步 Akaike 信息准则（stepAIC）建立去甲基化相关风险模型。
TET1 在肿瘤样本中的表达明显高于正常样本。晚期（III+IV）和高等级（G3+G4）的 HCC 患者的 TET1 表达高于早期（I+II）和低等级（G1+G2）的患者。高 TET1 表达的 HCC 样本的预后比低表达的差。高和低 TET1 表达组的免疫细胞浸润和对免疫治疗和化疗的反应存在明显差异。我们在高 vs. 低 TET1 表达组中鉴定了 90 个与 DNA 去甲基化相关的 DEGs。此外，我们基于包含 7 个关键预后基因（SERPINH1、CDC20、HACD2、SPHK1、UGT2B15、SLC1A5 和 CYP2C9）的 90 个 DEGs 建立了一个风险模型，该模型在预测 HCC 预后方面具有有效性和稳健性。
我们的研究表明 TET1 是 HCC 进展的潜在指标。TET1 密切参与免疫浸润和致癌途径的激活。DNA 去甲基化相关风险模型有望在临床上用于预测 HCC 预后。
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