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.

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

Department of Pathology,Shanghai Tenth People's Hospital,Tongji University School of Medicine,Shanghai 200072,China;Bio-X Center,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education),Shanghai Jiao Tong University,Shanghai 200000,China

当代医学科学(英文)

[1]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-.Hypomethylation of Thyroid Peroxidase as a Biomarker for Hepatocellular Carcinoma with Tumor Thrombosis)[J].当代医学科学(英文),2022(06):1248-1255

Hypomethylation

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