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We thank Chen and Lin for their interest in our article.1 They raised concerns about the comparison between α-fetoprotein (AFP) and the 5-hydroxymethylcytosine (5hmC)-based weighted diagnostic (wd)-scores,2 a debate worth further clarification.
First, it should be clarified that Chen and Lin’s description did not represent the overall picture of the wd-scores.1 The performance measures mentioned by Chen and Lin were specifically for distinguishing early hepatocellular carcinoma (HCC) and non-HCC (including not just chronic hepatitis B (CHB) virus infection but also benign liver lesions, liver cirrhosis (LC) and healthy controls) in the validation set. Notably, the 5hmC-based wd-scores consistently outperformed AFP in both training and validation sets for HCC versus non-HCC, early HCC versus CHB/LC, and early HCC versus controls (healthy individuals, benign liver lesions). Compared with AFP alone, the 5hmC-based wd-scores performed especially well when detecting early …
CH, WZ and JF are joint senior authors.
JC and ZZ contributed equally.
Contributors All authors contributed significantly to the work.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests The 5-hydroxymethylcytosine-Seal (5hmC-Seal) technology was invented by CH and was licensed by Shanghai Epican Genetech Co. Ltd. for clinical applications in human diseases from the University of Chicago. CH and WZ are shareholders of Shanghai Epican Genetech Co. Ltd. CH is a scientific founder of Accent Therapeutics, Inc., and a member of its scientific advisory board.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; internally peer reviewed.