General Surgery Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
Front Immunol. 2023 Jan 13;13:1091103. doi: 10.3389/fimmu.2022.1091103. eCollection 2022.
Although we had identified that the methylation of AHNAK was a good diagnostic marker for hepatopathy, here we speculate that there was also another marker, STAP1, whose methylation also involved in the detection of hepatopathy.
We investigated the methylation levels of the AHNAK and STAP1 in peripheral blood mononuclear cells of chronic hepatitis B (CHB) patients, compensatory liver cirrhosis (CLC) patients, decompensated liver cirrhosis (DCLC) patients, hepatocellular carcinoma (HCC) patients and healthy controls by methylation-specific PCR. We also evaluated the differences and changes of methylation and expression of AHNAK and STAP1 at different stages of liver disease using the TCGA and GEO public datasets.
Methylation level of STAP1 in PBMC was positively correlated with the course of liver cancer. The combination of AHNAK and STAP1 methylation was able to predict differrent HBV related hepatopathy. The GEO datasets also supported that the methylation of AHNAK and STAP1 was associated with different types of hepatopathy. The TCGA data showed that the levels of methylation and expression of STAP1 were down-regulated in HCC. We also found the STAP1 methylation level in PBMC and T cells was associated with age, gender, alcohol drinking and anti-HBe. Hyper-methylation of STAP1 was correlated with the poor prognosis of patients but its expression had no association.
We concluded that combination of AHNAK and STAP1 methylation in peripheral blood immune cells can be used as a diagnostic marker for HBV related hepatopathy and STAP1 methylation may be a potential prognostic marker for HBV related HCC. Our clinical study registration number was ChiCTR2000039860.
尽管我们已经确定 AHNAK 的甲基化是肝疾病的良好诊断标志物，但在这里我们推测还有另一个标志物 STAP1，其甲基化也涉及肝疾病的检测。
我们通过甲基化特异性 PCR 检测慢性乙型肝炎 (CHB) 患者、代偿性肝硬化 (CLC) 患者、失代偿性肝硬化 (DCLC) 患者、肝细胞癌 (HCC) 患者和健康对照者外周血单个核细胞中 AHNAK 和 STAP1 的甲基化水平。我们还使用 TCGA 和 GEO 公共数据集评估了不同阶段肝疾病中 AHNAK 和 STAP1 的甲基化和表达的差异和变化。
PBMC 中 STAP1 的甲基化水平与肝癌的病程呈正相关。AHNAK 和 STAP1 甲基化的组合能够预测不同的乙型肝炎相关肝疾病。GEO 数据集也支持 AHNAK 和 STAP1 的甲基化与不同类型的肝疾病有关。TCGA 数据显示，HCC 中 STAP1 的甲基化和表达水平下调。我们还发现 PBMC 和 T 细胞中的 STAP1 甲基化水平与年龄、性别、饮酒和抗-HBe 有关。STAP1 的高甲基化与患者的预后不良相关，但与其表达无关。
我们的结论是，外周血免疫细胞中 AHNAK 和 STAP1 甲基化的组合可作为乙型肝炎相关肝疾病的诊断标志物，STAP1 甲基化可能是乙型肝炎相关 HCC 的潜在预后标志物。我们的临床研究注册号为 ChiCTR2000039860。
