Efficacy of ctDNA methylation combined with traditional detection modality to detect liver cancer among high-risk patients:A multicenter diagnostic trial

Objective:Circulating tumor DNA(ctDNA)and alpha-fetoprotein(AFP)plus ultrasound(US)have been considered to have high diagnostic accuracy for cancer detection,however,the efficacy of ctDNA methylation combined with the traditional detection modality of liver cancer has not been tested in a Chinese independent cohort.Methods:The high-risk individuals aged between 35 and 70 years who were diagnosed with liver cirrhosis or had moderate and severe fatty liver were eligible for inclusion.All participants were invited to receive a traditional examination[referring to AFP plus US],and ctDNA methylation,respectively.The sensitivity and specificity of different diagnostic tools were calculated.The logistic regression model was applied to estimate the area under the curve(AUC),which was further validated by 10-fold internal cross-validation.Results:A total of 1,205 individuals were recruited in our study,and 39 participants were diagnosed with liver cancer.The sensitivity of AFP,US,US plus AFP,and the combination of US,AFP,and ctDNA methylation was33.33%,56.41%,66.67%,and 87.18%,respectively.The corresponding specificity of AFP,US,US plus AFP,and the combination of all modalities was 98.20%,99.31%,97.68%,and 97.68%,respectively.The AUCs of AFP,US,US plus AFP,and the combination of AFP,US,and ctDNA methylation were 65.77%,77.86%,82.18%,and92.43%,respectively.The internally validated AUCs of AFP,US,US plus AFP,and the combination of AFP,US,and ctDNA methylation were 67.57%,83.26%,86.54%,and 93.35%,respectively.Conclusions:The ctDNA methylation is a good complementary to AFP and US for the detection of liver cancer.