Article Text

Download PDFPDF
Reply to ‘Are the 5-hydroxymethylcytosine-based wd-scores really superior over α-fetoprotein for the early diagnosis of hepatocellular carcinoma?’
  1. Jiabin Cai1,2,
  2. Zhou Zhang3,
  3. Chuan He4,
  4. Wei Zhang3,
  5. Jia Fan1,2
  1. 1 Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
  2. 2 Key Laboratory of Medical Epigenetics and Metabolism, Institute of Biomedical Sciences, Fudan University, Shanghai, China
  3. 3 Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
  4. 4 Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, and the Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois, USA
  1. Correspondence to Dr Jia Fan, Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China; fan.jia{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

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 …

View Full Text


  • 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.