Title: Identification of differentially methylated regions associated with both liver fibrosis and
hepatocellular carcinoma
Version: 0 Date: 21 Jun 2023
Reviewer's report:
In this manuscript the authors described identification of 17 differentially methylated regions
(DMRs) associated with liver fibrosis and hepatocellular carcinoma in humans by searching
different publicly available databases. They found 12 hypomethylated and 5 hypermethylated
DMRs in both cirrhosis and HCC, suggesting that aberrations in DNA methylations occurs
before HCC development.
o This study is based totally on database search. The authors did not validate DMR of any genes
in primary tumors or cirrhotic livers of human and/or animal origins.
• The authors did not provide any experimental evidence demonstrating that the differential
methylation of ELF1, NFIX, HDAC4, KAZN, TNNT3, and ALDH3B2 are causally linked to
fibrogenesis or hepatocarcinogenesis.
• It would be important also to determine whether there is any correlation between differential
methylation of the critical genes they identified with their transcript levels by searching publicly
available databases.
• Do any these genes are differentially methylated and/or expressed in any animal model of
fibrosis?
• It is not clear what the authors meant by “deteriorate” in this sentence “These genes could
deteriorate transcriptional regulation, alter the cytoskeleton, or decrease detoxification, resulting
in the development of liver fibrosis and consequent HCC (Fig. 5)”.
• Figure legends are too brief.
• In Fig. 5, significance of red and black fonts for different genes are not described. Also, the
pictures of the cirrhotic liver and HCC are blurry.
Title: Identification of differentially methylated regions associated with both liver fibrosis and
hepatocellular carcinoma
Version: 0 Date: 21 Jun 2023
Reviewer's report:
In this manuscript the authors described identification of 17 differentially methylated regions
(DMRs) associated with liver fibrosis and hepatocellular carcinoma in humans by searching
different publicly available databases. They found 12 hypomethylated and 5 hypermethylated
DMRs in both cirrhosis and HCC, suggesting that aberrations in DNA methylations occurs
before HCC development.
o This study is based totally on database search. The authors did not validate DMR of any genes
in primary tumors or cirrhotic livers of human and/or animal origins.
• The authors did not provide any experimental evidence demonstrating that the differential
methylation of ELF1, NFIX, HDAC4, KAZN, TNNT3, and ALDH3B2 are causally linked to
fibrogenesis or hepatocarcinogenesis.
• It would be important also to determine whether there is any correlation between differential
methylation of the critical genes they identified with their transcript levels by searching publicly
available databases.
• Do any these genes are differentially methylated and/or expressed in any animal model of
fibrosis?
• It is not clear what the authors meant by “deteriorate” in this sentence “These genes could
deteriorate transcriptional regulation, alter the cytoskeleton, or decrease detoxification, resulting
in the development of liver fibrosis and consequent HCC (Fig. 5)”.
• Figure legends are too brief.
• In Fig. 5, significance of red and black fonts for different genes are not described. Also, the
pictures of the cirrhotic liver and HCC are blurry.
Please review this paper.
user
Title: Identification of differentially methylated regions associated with both liver fibrosis and
hepatocellular carcinoma
Version: 0 Date: 21 Jun 2023
Reviewer's report:
In this manuscript the authors described identification of 17 differentially methylated regions
(DMRs) associated with liver fibrosis and hepatocellular carcinoma in humans by searching
different publicly available databases. They found 12 hypomethylated and 5 hypermethylated
DMRs in both cirrhosis and HCC, suggesting that aberrations in DNA methylations occurs
before HCC development.
o This study is based totally on database search. The authors did not validate DMR of any genes
in primary tumors or cirrhotic livers of human and/or animal origins.
• The authors did not provide any experimental evidence demonstrating that the differential
methylation of ELF1, NFIX, HDAC4, KAZN, TNNT3, and ALDH3B2 are causally linked to
fibrogenesis or hepatocarcinogenesis.
• It would be important also to determine whether there is any correlation between differential
methylation of the critical genes they identified with their transcript levels by searching publicly
available databases.
• Do any these genes are differentially methylated and/or expressed in any animal model of
fibrosis?
• It is not clear what the authors meant by “deteriorate” in this sentence “These genes could
deteriorate transcriptional regulation, alter the cytoskeleton, or decrease detoxification, resulting
in the development of liver fibrosis and consequent HCC (Fig. 5)”.
• Figure legends are too brief.
• In Fig. 5, significance of red and black fonts for different genes are not described. Also, the
pictures of the cirrhotic liver and HCC are blurry.
assistant