Reviewer’s report
Title: 
Colorectal cancer screening using a stool DNA-based SDC2 methylation
test: a multicenter, prospective trial
Version: 
0 
Date: 
03 Feb 2021
Reviewer's report:
As the authors mentioned in this manuscript and their previous reports, I also
think that evaluation of a stool DNA methylation is an attractive target for early
CRC screening and EarlyTect-Colon Cancer is an interesting product. If this
strategy proves to be useful, it will be beneficial to many people. This study
protocol is generally fine. However, I think that some additional information
require to make it more meaningful.
(1) Could SCD2 methylation status and accuracy of this product be affected by
age, gender, or race? If these factors have been known to affect the methylation
in previous analyses, please state in discussion.
(2) The authors include patients with IBD. Could fecal methylated SDC2 be
influenced by IBD not CRC? Please comment.
(3) How many times do participants collect stool samples? Once or more? If the
sample is collected only once despite being asymptomatic, I am concerned that
the accuracy may not guaranteed like fecal occult blood test. On the other hand,
the amount to be provided 20g seems to be higher than other similar test. Is this
because of the product? Please indicate evidences that the authors decided this
protocol of collecting stool.
(4) If the aim of this trial is to validate in asymptomatic population, please also
state it in participant selection criteria.
(5) Niu F et al reported berberine affected fecal detection of methylated SDC2
(Cancer Epidemiol Biomarkers Prev, 2017). Is there any daily medication that
interferes the methylation? If some kind of the drug exists, I think its history is
also better to be considered in criteria and recorded as clinical background.
(6) As the above report, some similar clinical trials of fecal methylated SDC2
have been reported. What are the strengths of this study and product compared
with others? How do you suggest this study protocol will help to improve the
standard of medical research?
Publons Reviewer Recognition
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Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Reviewer’s report
Title: 
Colorectal cancer screening using a stool DNA-based SDC2 methylation
test: a multicenter, prospective trial
Version: 
0 
Date: 
03 Feb 2021
Reviewer's report:
As the authors mentioned in this manuscript and their previous reports, I also
think that evaluation of a stool DNA methylation is an attractive target for early
CRC screening and EarlyTect-Colon Cancer is an interesting product. If this
strategy proves to be useful, it will be beneficial to many people. This study
protocol is generally fine. However, I think that some additional information
require to make it more meaningful.
(1) Could SCD2 methylation status and accuracy of this product be affected by
age, gender, or race? If these factors have been known to affect the methylation
in previous analyses, please state in discussion.
(2) The authors include patients with IBD. Could fecal methylated SDC2 be
influenced by IBD not CRC? Please comment.
(3) How many times do participants collect stool samples? Once or more? If the
sample is collected only once despite being asymptomatic, I am concerned that
the accuracy may not guaranteed like fecal occult blood test. On the other hand,
the amount to be provided 20g seems to be higher than other similar test. Is this
because of the product? Please indicate evidences that the authors decided this
protocol of collecting stool.
(4) If the aim of this trial is to validate in asymptomatic population, please also
state it in participant selection criteria.
(5) Niu F et al reported berberine affected fecal detection of methylated SDC2
(Cancer Epidemiol Biomarkers Prev, 2017). Is there any daily medication that
interferes the methylation? If some kind of the drug exists, I think its history is
also better to be considered in criteria and recorded as clinical background.
(6) As the above report, some similar clinical trials of fecal methylated SDC2
have been reported. What are the strengths of this study and product compared
with others? How do you suggest this study protocol will help to improve the
standard of medical research?
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
Please review this paper.
user
Reviewer’s report
Title: 
Colorectal cancer screening using a stool DNA-based SDC2 methylation
test: a multicenter, prospective trial
Version: 
0 
Date: 
03 Feb 2021
Reviewer's report:
As the authors mentioned in this manuscript and their previous reports, I also
think that evaluation of a stool DNA methylation is an attractive target for early
CRC screening and EarlyTect-Colon Cancer is an interesting product. If this
strategy proves to be useful, it will be beneficial to many people. This study
protocol is generally fine. However, I think that some additional information
require to make it more meaningful.
(1) Could SCD2 methylation status and accuracy of this product be affected by
age, gender, or race? If these factors have been known to affect the methylation
in previous analyses, please state in discussion.
(2) The authors include patients with IBD. Could fecal methylated SDC2 be
influenced by IBD not CRC? Please comment.
(3) How many times do participants collect stool samples? Once or more? If the
sample is collected only once despite being asymptomatic, I am concerned that
the accuracy may not guaranteed like fecal occult blood test. On the other hand,
the amount to be provided 20g seems to be higher than other similar test. Is this
because of the product? Please indicate evidences that the authors decided this
protocol of collecting stool.
(4) If the aim of this trial is to validate in asymptomatic population, please also
state it in participant selection criteria.
(5) Niu F et al reported berberine affected fecal detection of methylated SDC2
(Cancer Epidemiol Biomarkers Prev, 2017). Is there any daily medication that
interferes the methylation? If some kind of the drug exists, I think its history is
also better to be considered in criteria and recorded as clinical background.
(6) As the above report, some similar clinical trials of fecal methylated SDC2
have been reported. What are the strengths of this study and product compared
with others? How do you suggest this study protocol will help to improve the
standard of medical research?
Publons Reviewer Recognition
. Springer Nature can send verification of this
review directly to Publons (a subsidiary of Clarivate Analytics). If you would
like to take advantage of this service, please click on the “Yes” option below.
Your name, email address, title of the reviewed manuscript, name of the journal,
and date of your review submission (the “Review Data”) will then be transmitted
to Publons after the final decision on the manuscript has been made. If you have
already registered at Publons, they will notify you of the receipt of this review
and update your profile 
as per your settings and their policy. If you are not
registered with Publons, you will receive an email from them asking you to
register in order for them to be able to recognize your review on your new
profile page. Publons may use the Review Data to generate derivative metadata
for the benefit of Publons and you as a reviewer, carefully considering the
sensitivity of such information. For example, Publons may verify your record as
a reviewer by updating your profile published on its webservice if you have
registered for such service or help editors to identify candidate reviewers. Please
find the details of processing in Publons’ privacy policy
https://publons.com/about/terms
Yes
Declaration of competing interests
Please complete a declaration of competing
interests, considering the following questions:
1
. 
Have you in the past five years received reimbursements, fees, funding, or
salary from an organisation that may in any way gain or lose financially
from the publication of this manuscript, either now or in the future?
2
. 
Do you hold any stocks or shares in an organisation that may in any way
gain or lose financially from the publication of this manuscript, either now
or in the future?
3
. 
Do you hold or are you currently applying for any patents relating to the
content of the manuscript?
4
. 
Have you received reimbursements, fees, funding, or salary from an
organization that holds or has applied for patents relating to the content of
the manuscript?
5
. 
Do you have any other financial competing interests?
6
. 
Do you have any non-financial competing interests in relation to this
paper?
If you can answer no to all of the above, write 'I declare that I have no competing
interests' below. If your reply is yes to any, please give details below.
I declare that I have no competing interests.
Reviewer Publication Consent.
 I agree for my report to be made available
under an Open Access Creative Commons CC-BY License (
http://creativecommons.org/licenses/by/4.0
) if this manuscript is accepted for
publication. Any comments that I do not wish to be included in the published
report have been included as confidential comments to the editor, which will not
be published.
If you are not happy for us to publish this report, please contact the
editorial office before completing the review.
If you wish, you can include your
name in your published report. Please note you must decide whether to include
your name at the start of the process and confirm this decision whenever
prompted. If you change your decision later, we will not be able to publish your
name.
I agree to the terms of the CC-BY 4.0 license; please 
do not
 publish my name
with my report. (default)
Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
Yes
Are the methods sufficiently described to allow the study to be repeated?
Yes
Is the use of statistics and treatment of uncertainties appropriate?
Yes
Is the presentation of the work clear?
Yes
Are the images in this manuscript (including electrophoretic gels and blots) free
from apparent manipulation?
Yes
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