Reviewer ’s report  
 
Title: Unique characteristics of CpG island methylator phenotype (CIMP) in a Chinese 
population  
with colorectal cancer  
 
Version: 0 Date: 22 Jul 2019  
 
Reviewer: Yuqing Cheng  
 
Reviewer's report:  
 
The authors investigated the incidence of CIMP, BRAF/KRAS mutations and MSI in a Chinese 
population  and analyzed the association of the CIMP phenotype with clinicopathological and 
molecular features. The detection of the CIMP -high phenotype suggested the presence of a 
subset of CRC patients in the younger age, female predominance, and proximal tumor loc ation. 
The results of the study help to illustrate the molecular characteristics of CRC in the Chinese 
population. I have a few comments as follows:  
1. The results and conclusions sections in the abstract should be focused on the study itself. The 
statemen ts such as "this is the first study to ..." and "different genetic backgrounds and lifestyle 
habits may contribute to..." should be more suitable in the discussion section.  
2. It is well known that Braf mutation is the main cause of sporadic MSI -H CRC (abo ut 80% of 
the overall MSI -H CRC) and MLH1 methylation, so that the obvious discrepancy between the 
frequency of Braf mutation (3/401) and MSI -H (5/82), MLH1 methylation (15/401) should be 
discussed in details.  
3. The subgroup classified by the CIMP -3 panel  showed no association with important molecular 
and clinicopathological features such as the MSI status, BRAF/KRAS mutation, and pathologic 
stage. The associations of the CIMP phenotype classified by different panels with the T -N-M 
stage, histopathology cl assification, or prognosis were not clear. It is difficult for me to concur 
the statement that the "CIMP -3 panel outperformed the CIMP -1 and CIMP -2 panels ".  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Needs some language corrections before being published  
 
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, fund ing, 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, w rite '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.  
 
I agree to the open peer review policy of the journal. I understand that my name will be includ ed 
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Unique characteristics of CpG island methylator phenotype (CIMP) in a Chinese 
population  
with colorectal cancer  
 
Version: 0 Date: 22 Jul 2019  
 
Reviewer: Yuqing Cheng  
 
Reviewer's report:  
 
The authors investigated the incidence of CIMP, BRAF/KRAS mutations and MSI in a Chinese 
population  and analyzed the association of the CIMP phenotype with clinicopathological and 
molecular features. The detection of the CIMP -high phenotype suggested the presence of a 
subset of CRC patients in the younger age, female predominance, and proximal tumor loc ation. 
The results of the study help to illustrate the molecular characteristics of CRC in the Chinese 
population. I have a few comments as follows:  
1. The results and conclusions sections in the abstract should be focused on the study itself. The 
statemen ts such as "this is the first study to ..." and "different genetic backgrounds and lifestyle 
habits may contribute to..." should be more suitable in the discussion section.  
2. It is well known that Braf mutation is the main cause of sporadic MSI -H CRC (abo ut 80% of 
the overall MSI -H CRC) and MLH1 methylation, so that the obvious discrepancy between the 
frequency of Braf mutation (3/401) and MSI -H (5/82), MLH1 methylation (15/401) should be 
discussed in details.  
3. The subgroup classified by the CIMP -3 panel  showed no association with important molecular 
and clinicopathological features such as the MSI status, BRAF/KRAS mutation, and pathologic 
stage. The associations of the CIMP phenotype classified by different panels with the T -N-M 
stage, histopathology cl assification, or prognosis were not clear. It is difficult for me to concur 
the statement that the "CIMP -3 panel outperformed the CIMP -1 and CIMP -2 panels ".  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Needs some language corrections before being published  
 
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, fund ing, 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, w rite '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.  
 
I agree to the open peer review policy of the journal. I understand that my name will be includ ed 
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Unique characteristics of CpG island methylator phenotype (CIMP) in a Chinese 
population  
with colorectal cancer  
 
Version: 0 Date: 22 Jul 2019  
 
Reviewer: Yuqing Cheng  
 
Reviewer's report:  
 
The authors investigated the incidence of CIMP, BRAF/KRAS mutations and MSI in a Chinese 
population  and analyzed the association of the CIMP phenotype with clinicopathological and 
molecular features. The detection of the CIMP -high phenotype suggested the presence of a 
subset of CRC patients in the younger age, female predominance, and proximal tumor loc ation. 
The results of the study help to illustrate the molecular characteristics of CRC in the Chinese 
population. I have a few comments as follows:  
1. The results and conclusions sections in the abstract should be focused on the study itself. The 
statemen ts such as "this is the first study to ..." and "different genetic backgrounds and lifestyle 
habits may contribute to..." should be more suitable in the discussion section.  
2. It is well known that Braf mutation is the main cause of sporadic MSI -H CRC (abo ut 80% of 
the overall MSI -H CRC) and MLH1 methylation, so that the obvious discrepancy between the 
frequency of Braf mutation (3/401) and MSI -H (5/82), MLH1 methylation (15/401) should be 
discussed in details.  
3. The subgroup classified by the CIMP -3 panel  showed no association with important molecular 
and clinicopathological features such as the MSI status, BRAF/KRAS mutation, and pathologic 
stage. The associations of the CIMP phenotype classified by different panels with the T -N-M 
stage, histopathology cl assification, or prognosis were not clear. It is difficult for me to concur 
the statement that the "CIMP -3 panel outperformed the CIMP -1 and CIMP -2 panels ".  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscr ipt: 
 
Needs some language corrections before being published  
 
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, fund ing, 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, w rite '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.  
 
I agree to the open peer review policy of the journal. I understand that my name will be includ ed 
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. 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/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as  confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant