Title: The m6A/m5C/m1A regulator genes Signature Reveals The Prognosis and Related with
Immune Microenvironment for Hepatocellular Carcinoma
Version: 3 Date: 08 Mar 2023
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The manuscript was a bioinformatics study focused on the role of
RNA modification proteins in the pathogenesis of HCC.  Evidence is presented that shows a
correlation between the differential expression of YTHDF1, YBX1, TRMT10C and TRMT61A
and HCC survival.  However, very little is said about the putative mechanisms whereby these
differentially expressed genes contribute to hepatocarcinogenesis, nor any mention of them as
potential biomarkers in blood because they have all been documented to be secreted.  It is not
clear that these proteins would be better than existing immune based markers associated with
HCC. Further, these differentially expressed proteins have been shown earlier to contribute to
the pathogenesis of HCC, so it is not clear how much new conceptual ground is provided by
this work.
REQUESTED REVISIONS:
How do the results of this study improve our ability to develop biomarkers since nothing is said
about generating ELISAs for clinical samples?  What new conceptual ideas are presented here?
What about the mechanisms whereby these up-regulated proteins contribute to HCC and their
rationale for further development as biomarkers?
ADDITIONAL REQUESTS/SUGGESTIONS:
Provide rationale to suggest that correlations presented in the paper have a biological basis for
cause and effect.  Are these correlations only present in tumor bearing patients, or do they occur
in patients with chronic liver disease and no HCC?"
Title: The m6A/m5C/m1A regulator genes Signature Reveals The Prognosis and Related with
Immune Microenvironment for Hepatocellular Carcinoma
Version: 3 Date: 08 Mar 2023
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The manuscript was a bioinformatics study focused on the role of
RNA modification proteins in the pathogenesis of HCC.  Evidence is presented that shows a
correlation between the differential expression of YTHDF1, YBX1, TRMT10C and TRMT61A
and HCC survival.  However, very little is said about the putative mechanisms whereby these
differentially expressed genes contribute to hepatocarcinogenesis, nor any mention of them as
potential biomarkers in blood because they have all been documented to be secreted.  It is not
clear that these proteins would be better than existing immune based markers associated with
HCC. Further, these differentially expressed proteins have been shown earlier to contribute to
the pathogenesis of HCC, so it is not clear how much new conceptual ground is provided by
this work.
REQUESTED REVISIONS:
How do the results of this study improve our ability to develop biomarkers since nothing is said
about generating ELISAs for clinical samples?  What new conceptual ideas are presented here?
What about the mechanisms whereby these up-regulated proteins contribute to HCC and their
rationale for further development as biomarkers?
ADDITIONAL REQUESTS/SUGGESTIONS:
Provide rationale to suggest that correlations presented in the paper have a biological basis for
cause and effect.  Are these correlations only present in tumor bearing patients, or do they occur
in patients with chronic liver disease and no HCC?"
Please review this paper.
user
Title: The m6A/m5C/m1A regulator genes Signature Reveals The Prognosis and Related with
Immune Microenvironment for Hepatocellular Carcinoma
Version: 3 Date: 08 Mar 2023
Reviewer's report:
"PEER REVIEWER ASSESSMENTS:
OBJECTIVE - Full research articles: is there a clear objective that addresses a testable research
question(s) (brief or other article types: is there a clear objective)?
Yes - there is a clear objective
DESIGN - Is the current approach (including controls and analysis protocols) appropriate for
the objective?
Yes - the approach is appropriate
EXECUTION - Are the experiments and analyses performed with technical rigor to allow
confidence in the results?
No - there are minor issues
STATISTICS - Is the use of statistics in the manuscript appropriate?
Yes - appropriate statistical analyses have been used in the study
INTERPRETATION - Is the current interpretation/discussion of the results reasonable and not
overstated?
No - there are minor issues
OVERALL MANUSCRIPT POTENTIAL - Is the current version of this work technically
sound? If not, can revisions be made to make the work technically sound?
Probably - with minor revisions
PEER REVIEWER COMMENTS:
GENERAL COMMENTS: The manuscript was a bioinformatics study focused on the role of
RNA modification proteins in the pathogenesis of HCC.  Evidence is presented that shows a
correlation between the differential expression of YTHDF1, YBX1, TRMT10C and TRMT61A
and HCC survival.  However, very little is said about the putative mechanisms whereby these
differentially expressed genes contribute to hepatocarcinogenesis, nor any mention of them as
potential biomarkers in blood because they have all been documented to be secreted.  It is not
clear that these proteins would be better than existing immune based markers associated with
HCC. Further, these differentially expressed proteins have been shown earlier to contribute to
the pathogenesis of HCC, so it is not clear how much new conceptual ground is provided by
this work.
REQUESTED REVISIONS:
How do the results of this study improve our ability to develop biomarkers since nothing is said
about generating ELISAs for clinical samples?  What new conceptual ideas are presented here?
What about the mechanisms whereby these up-regulated proteins contribute to HCC and their
rationale for further development as biomarkers?
ADDITIONAL REQUESTS/SUGGESTIONS:
Provide rationale to suggest that correlations presented in the paper have a biological basis for
cause and effect.  Are these correlations only present in tumor bearing patients, or do they occur
in patients with chronic liver disease and no HCC?"
assistant