Methylation-sensitive high-resolution melting analysis of the USP44 promoter can detect early-stage hepatocellular carcinoma in blood samples
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Hepatocellular carcinoma (HCC) is dangerous cancer that oftenevades early detection because it is asymptomatic and an effectivedetection method is lacking. For people with chronic liverinflammation who are at high risk of developing HCC, a sensitivedetection method for HCC is needed. In a meta-analysisof The Cancer Genome Atlas pan-cancer methylation database,we identified a CpG island in the USP44 promoter that is methylatedspecifically in HCC. We developed methylation-sensitivehigh-resolution melting (MS-HRM) analysis to measure themethylation levels of the USP promoter in cell-free DNA isolatedfrom patients. Our MS-HRM assay correctly identified 40% ofpatients with early-stage HCC, whereas the α-fetoprotein test,which is currently used to detect HCC, correctly identified only25% of early-stage HCC patients. These results demonstratethat USP44 MS-HRM analysis is suitable for HCC surveillance.
Abstract
Hepatocellular carcinoma (HCC) is dangerous cancer that oftenevades early detection because it is asymptomatic and an effectivedetection method is lacking. For people with chronic liverinflammation who are at high risk of developing HCC, a sensitivedetection method for HCC is needed. In a meta-analysisof The Cancer Genome Atlas pan-cancer methylation database,we identified a CpG island in the USP44 promoter that is methylatedspecifically in HCC. We developed methylation-sensitivehigh-resolution melting (MS-HRM) analysis to measure themethylation levels of the USP promoter in cell-free DNA isolatedfrom patients. Our MS-HRM assay correctly identified 40% ofpatients with early-stage HCC, whereas the α-fetoprotein test,which is currently used to detect HCC, correctly identified only25% of early-stage HCC patients. These results demonstratethat USP44 MS-HRM analysis is suitable for HCC surveillance.
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