Reviewer ’s report  
 
Title: Prognostic value of peripheral blood natural killer cells in colorectal cancer  
 
Version: 0 Date: 02 Dec 2019  
 
Reviewer: Eric Smith  
 
Reviewer's report:  
 
In general this article would benefit from extensive editing for English.  
 
 
Several other issues require attention - 
 
1. Did patients with rectal cancer receive neoadjuvant/preoperative chemotherapy or 
chemoradiotherapy? If so, when was the blood sample taken? Before or after preoperative 
therapy?  
 
2. Does R0 refer to primary tumour or does it include resection of metastat ic disease? Please 
clarify.  
 
3. The abbreviations (eg CRP, NLR, PLR) that first appear in the Data Collection section of the 
Materials and Methods need defining.  
 
4. The method(s) used for the correlations that are presented in Table 3 don't appear to be 
described in the Material and Methods. The p -values should be adjusted for multiple 
comparisons using for example Benjamini -Hochberg correction.  
 
5. The median follow -up of 24 months (range 16 -28 months) seems very short for overall 
survival of R0 resected tum ours. Would it be more informative/appropriate to report disease -free 
or recurrence -free survival, rather than overall survival.  
 
6. In the results the authors state "There were 224 colon adenoma and 223 rectal adenoma". Do 
they mean adenocarcinoma?  
 
7. Can  the authors explain the rationale for using the median percentage value of NK cells, rather 
than some other cut -off? For the univariate and multivariable analyses, were the continuous or 
group data analysed for NK cells etc? Please define.  
 
8. In Table 2 T -stage is reported as T1+T2 v T1+T2. Needs correction/clarification? Same for 
Table 4.  
 
9. What clinical staging system was used? Do the authors have an explanation for why clinical 
stage was not an independent prognostic variable for overall survival? Leng th of follow -up? OS 
v DFS?  
10. T, N and M stage were not associated with overall survival. Do the authors have an 
explanation? Length of follow -up? OS v DFS?  
 
11. Coca et al report intratumoral infiltration of NK cells. Why would the authors expect 
numbers of peripheral blood NK cells to reflect intratumoral numbers? Requires further 
discussion.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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 manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in t he past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisat ion 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 reimbursemen ts, 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 t his 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.  
 
I agree to the open peer review policy of  the journal. I understan d that m y name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I a gree 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: Prognostic value of peripheral blood natural killer cells in colorectal cancer  
 
Version: 0 Date: 02 Dec 2019  
 
Reviewer: Eric Smith  
 
Reviewer's report:  
 
In general this article would benefit from extensive editing for English.  
 
 
Several other issues require attention - 
 
1. Did patients with rectal cancer receive neoadjuvant/preoperative chemotherapy or 
chemoradiotherapy? If so, when was the blood sample taken? Before or after preoperative 
therapy?  
 
2. Does R0 refer to primary tumour or does it include resection of metastat ic disease? Please 
clarify.  
 
3. The abbreviations (eg CRP, NLR, PLR) that first appear in the Data Collection section of the 
Materials and Methods need defining.  
 
4. The method(s) used for the correlations that are presented in Table 3 don't appear to be 
described in the Material and Methods. The p -values should be adjusted for multiple 
comparisons using for example Benjamini -Hochberg correction.  
 
5. The median follow -up of 24 months (range 16 -28 months) seems very short for overall 
survival of R0 resected tum ours. Would it be more informative/appropriate to report disease -free 
or recurrence -free survival, rather than overall survival.  
 
6. In the results the authors state "There were 224 colon adenoma and 223 rectal adenoma". Do 
they mean adenocarcinoma?  
 
7. Can  the authors explain the rationale for using the median percentage value of NK cells, rather 
than some other cut -off? For the univariate and multivariable analyses, were the continuous or 
group data analysed for NK cells etc? Please define.  
 
8. In Table 2 T -stage is reported as T1+T2 v T1+T2. Needs correction/clarification? Same for 
Table 4.  
 
9. What clinical staging system was used? Do the authors have an explanation for why clinical 
stage was not an independent prognostic variable for overall survival? Leng th of follow -up? OS 
v DFS?  
10. T, N and M stage were not associated with overall survival. Do the authors have an 
explanation? Length of follow -up? OS v DFS?  
 
11. Coca et al report intratumoral infiltration of NK cells. Why would the authors expect 
numbers of peripheral blood NK cells to reflect intratumoral numbers? Requires further 
discussion.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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 manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in t he past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisat ion 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 reimbursemen ts, 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 t his 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.  
 
I agree to the open peer review policy of  the journal. I understan d that m y name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I a gree 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: Prognostic value of peripheral blood natural killer cells in colorectal cancer  
 
Version: 0 Date: 02 Dec 2019  
 
Reviewer: Eric Smith  
 
Reviewer's report:  
 
In general this article would benefit from extensive editing for English.  
 
 
Several other issues require attention - 
 
1. Did patients with rectal cancer receive neoadjuvant/preoperative chemotherapy or 
chemoradiotherapy? If so, when was the blood sample taken? Before or after preoperative 
therapy?  
 
2. Does R0 refer to primary tumour or does it include resection of metastat ic disease? Please 
clarify.  
 
3. The abbreviations (eg CRP, NLR, PLR) that first appear in the Data Collection section of the 
Materials and Methods need defining.  
 
4. The method(s) used for the correlations that are presented in Table 3 don't appear to be 
described in the Material and Methods. The p -values should be adjusted for multiple 
comparisons using for example Benjamini -Hochberg correction.  
 
5. The median follow -up of 24 months (range 16 -28 months) seems very short for overall 
survival of R0 resected tum ours. Would it be more informative/appropriate to report disease -free 
or recurrence -free survival, rather than overall survival.  
 
6. In the results the authors state "There were 224 colon adenoma and 223 rectal adenoma". Do 
they mean adenocarcinoma?  
 
7. Can  the authors explain the rationale for using the median percentage value of NK cells, rather 
than some other cut -off? For the univariate and multivariable analyses, were the continuous or 
group data analysed for NK cells etc? Please define.  
 
8. In Table 2 T -stage is reported as T1+T2 v T1+T2. Needs correction/clarification? Same for 
Table 4.  
 
9. What clinical staging system was used? Do the authors have an explanation for why clinical 
stage was not an independent prognostic variable for overall survival? Leng th of follow -up? OS 
v DFS?  
10. T, N and M stage were not associated with overall survival. Do the authors have an 
explanation? Length of follow -up? OS v DFS?  
 
11. Coca et al report intratumoral infiltration of NK cells. Why would the authors expect 
numbers of peripheral blood NK cells to reflect intratumoral numbers? Requires further 
discussion.  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Unable to assess  
 
Are you able to assess any statistics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy 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 manuscript:  
 
Not suitable for publication unless extensively edited  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in t he past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financial ly from the 
publication of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisat ion 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 reimbursemen ts, 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 t his 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.  
 
I agree to the open peer review policy of  the journal. I understan d that m y name will be included 
on my report to the authors and, if the manuscript is accepted f or publication, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I a gree 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