Hypomethylation of Thyroid Peroxidase as a Biomarker for Hepatocellular Carcinoma with Tumor Thrombosis
作者机构:Department of PathologyShanghai Tenth People’s HospitalTongji University School of MedicineShanghai200072China Bio-X CenterKey Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai200000China
出 版 物:《Current Medical Science》 (当代医学科学(英文))
年 卷 期:2022年第42卷第6期
页 面:1248-1255页
核心收录:
学科分类:1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
主 题:thyroid hormones thyroid peroxidase hepatocellular carcinoma methylation tumor thrombosis
摘 要:Objective Thyroid hormones(THs)regulate multiple physiological activities in the liver,including cellular metabolism,differentiation,and cell growth,and play important roles in the pathogenesis of hepatocellular carcinoma(HCC).Thyroid peroxidase(TPO)is a key molecule involved in the THs synthesis and signaling pathway.As an epigenetic modification,DNA methylation has a critical role in tumorigenesis with diagnostic potential.However,the connection between THs and DNA methylation has been rarely investigated.Methods The methylation of key TH-related genes was analyzed by in-house epigenome-wide scanning,and we further analyzed the methylation levels of the TPO promotor in 164 sample pairs of HCC and adjacent non-cancerous tissues by Sequenom EpiTYPER assays,and evaluated their clinical implications.Results We identified that the methylation of the TPO promoter was downregulated in the HCC tissues(P0.0001)with a mean difference ranging from 18.5%to 22.3%.This methylation pattern correlated with several clinical factors,including a multi-satellite tumor,fibrous capsule,and the presence of tumor thrombus.The receiver operator characteristic(ROC)curve analysis further confirmed that the percent methylated reference(PMR)values for TPO were predictive of the tumor[the area under the curve(AUC)ranged from 0.755 to 0.818]and the thrombosis in the HCC patients(the AUC ranged from 0.706 to 0.777).Conclusion These findings demonstrated that epigenetic alterations of TPO,as indicated by the PMR values,were a potential biomarker for HCC patients with tumor thrombosis.