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We read with interest the recent article by Cai et al1 describing the development of 5-hydroxymethylcytosine (5hmC)-based wd-scores that have better accuracy in diagnosing early hepatocellular carcinoma (HCC) than does α-fetoprotein (AFP). Although several gene signatures have been published but not used in practice of early HCC diagnosis,2 this study showed the potential application of the 5hmC-based wd scores. However, several concerns remain that need to be clarified.
First, the wd-scores’ cut-off for early diagnosis of HCC, derived by the maximal Youden index and characterised by a sensitivity of 82.7% and a specificity of 76.4%, is suboptimal; this would result in missed diagnosis of early HCC in 17.3% of patients, and the corresponding …
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