Hypomethylation of Thyroid Peroxidase as a Biomarker for Hepatocellular Carcinoma with Tumor Thrombosis  

作　　者：Ru-ting XIE Qian-yu LI Xue-chen SUN Qing-jun ZHI Xiang-xiang HUANG Xing-chen ZHU Qi-zeng MIAO Dai-zhan ZHOU Dong-yan HAN 

机构地区：[1]Department of Pathology,Shanghai Tenth People’s Hospital,Tongji University School of Medicine,Shanghai,200072,China [2]Bio-X Center,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education),Shanghai Jiao Tong University,Shanghai,200000,China

出　　处：《Current Medical Science》2022年第6期1248-1255,共8页当代医学科学（英文）

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(P<0.0001)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.

关 键 词：thyroid hormones thyroid peroxidase hepatocellular carcinoma METHYLATION tumor thrombosis 

分 类 号：R735.7[医药卫生—肿瘤]