Reviewer ’s report  
 
Title: Prognostic value of peripheral blood natural killer cells in colorectal cancer  
 
Version: 0 Date: 14 Nov 2019  
 
Reviewer: Saikiran Raghavapuram  
 
Reviewer's report:  
 
Authors have written about the survival effect of NK cells in patients with colon cancer. It's a 
retrospective study. The a rticle may need following corrections:  
 
1) On page 5 under the section of data collection, "were extracted" was used twice. I suggest 
removing the "were extracted" from the first sentence and just write as:" The clinicopathological 
features of CRC includi ng" . In the same paragraph, it is better to expand the abbreviations of 
CRP,hsCRP, NLR, PLR, CRP/ALB ratio in the paragraph itself in addition to the expansion of 
these under the table 2 as done by the authors.  
 
2) It is noted that the 447 patient charts from January 2015 to Oct 2018 were considered. But 
how many of these patients were seen close to Oct 2018 was not mentioned. This matters 
because if there are large number of patients that are seen close to end of study period that is Oct 
2018, the results  of their follow up would be skewed.  
 
3) In the first paragraph of results section under "clinic characteristics of study population", 
second line should say 224 colon cancer (not adenoma) and 224 rectal cancer ( not rectal 
adenoma). Nomenclature should change from 'adenoma' to 'cancer' and al so appropriate space 
should be given. Also, its "clinic characteristics of study population " not populations as 
population is ltself pleural.  
  
4) Among 60 patients who died, it would be useful to know how many of them were diagnosed 
with colon cancer yea r wise (how many of those were diagnosed in 2015, 2016,2017 and in 
2018). Also a sub group analysis of NK cells in those 60 compared to live 387 patients with their 
year of diagnosis would be more informative.  
 
5) Any explanation from the authors as to w hy the NK cells percentage does not correlate with 
survival time in patients with rectal cancer when one of the study that is quoted by Coyle etal 
actually found improved survival in rectal cancer patients. (Natural killer -like signature observed 
post ther apy in locally advanced rectal cancer is a determinant of pathological response and 
improved survival.Alderdice M1, Dunne PD2, Cole AJ2,3, O'Reilly PG2, McArt DG1, Bingham 
V1, Fuchs MA1, McQuaid S1, Loughrey MB2,4, Murray GI5, Samuel LM6, Lawler M2, Wilson  
RH2,3, Salto -Tellez M1,2,4, Coyle VM2,3).  
 
6) In the paragraph under the heading "Association of NK cell with the clinicopathological 
features" the following line "The association of NK cells with patient age, gender ...were 
analysed (not analysis).  
7) In first sentence of page 9, it should be "joined", not "jointed".  
 
8) In page 9 discussion section, line 7 instead of "patients, they" write as "patients and found". 
Also in line 9, "inconsistent resulted also reported" should be followed by a period, not comma.  
 
9) In page 10, third paragraph line in placed of "increased prognostic value" it should be "can 
increase the prognostic value".  
 
10) In page 11, line 3, it should be " this study was a retrospective design which may lead to 
selection bias". In the  same paragraph in line 5 "median follow up of 24 months". This should be 
followed by a period, not coma with the sentence that has to follow be written as " the prognostic 
value of NK cells on long term survival still need to be investigated in future stu dies". In the 
same paragraph line 7 it should be written as" which have different antitumor activity, not 'has'. 
In line 9, it should be "future studies".  
 
11) Under conclusion section, in line 3, "could increase (not increased) the prognostic valve". In 
the same line, the following sentence should be corrected as follows "However, future studies are 
needed in order to verify our results"  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work includ e 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 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:  
 
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, f ees, funding, or salary 
from an organisation that may in any way gain or lose financially from the 
publi cation of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat 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 curr ently 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.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named rep ort 
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 understa nd that any comments 
which I do not wish to be included in my named report can be in cluded 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: 14 Nov 2019  
 
Reviewer: Saikiran Raghavapuram  
 
Reviewer's report:  
 
Authors have written about the survival effect of NK cells in patients with colon cancer. It's a 
retrospective study. The a rticle may need following corrections:  
 
1) On page 5 under the section of data collection, "were extracted" was used twice. I suggest 
removing the "were extracted" from the first sentence and just write as:" The clinicopathological 
features of CRC includi ng" . In the same paragraph, it is better to expand the abbreviations of 
CRP,hsCRP, NLR, PLR, CRP/ALB ratio in the paragraph itself in addition to the expansion of 
these under the table 2 as done by the authors.  
 
2) It is noted that the 447 patient charts from January 2015 to Oct 2018 were considered. But 
how many of these patients were seen close to Oct 2018 was not mentioned. This matters 
because if there are large number of patients that are seen close to end of study period that is Oct 
2018, the results  of their follow up would be skewed.  
 
3) In the first paragraph of results section under "clinic characteristics of study population", 
second line should say 224 colon cancer (not adenoma) and 224 rectal cancer ( not rectal 
adenoma). Nomenclature should change from 'adenoma' to 'cancer' and al so appropriate space 
should be given. Also, its "clinic characteristics of study population " not populations as 
population is ltself pleural.  
  
4) Among 60 patients who died, it would be useful to know how many of them were diagnosed 
with colon cancer yea r wise (how many of those were diagnosed in 2015, 2016,2017 and in 
2018). Also a sub group analysis of NK cells in those 60 compared to live 387 patients with their 
year of diagnosis would be more informative.  
 
5) Any explanation from the authors as to w hy the NK cells percentage does not correlate with 
survival time in patients with rectal cancer when one of the study that is quoted by Coyle etal 
actually found improved survival in rectal cancer patients. (Natural killer -like signature observed 
post ther apy in locally advanced rectal cancer is a determinant of pathological response and 
improved survival.Alderdice M1, Dunne PD2, Cole AJ2,3, O'Reilly PG2, McArt DG1, Bingham 
V1, Fuchs MA1, McQuaid S1, Loughrey MB2,4, Murray GI5, Samuel LM6, Lawler M2, Wilson  
RH2,3, Salto -Tellez M1,2,4, Coyle VM2,3).  
 
6) In the paragraph under the heading "Association of NK cell with the clinicopathological 
features" the following line "The association of NK cells with patient age, gender ...were 
analysed (not analysis).  
7) In first sentence of page 9, it should be "joined", not "jointed".  
 
8) In page 9 discussion section, line 7 instead of "patients, they" write as "patients and found". 
Also in line 9, "inconsistent resulted also reported" should be followed by a period, not comma.  
 
9) In page 10, third paragraph line in placed of "increased prognostic value" it should be "can 
increase the prognostic value".  
 
10) In page 11, line 3, it should be " this study was a retrospective design which may lead to 
selection bias". In the  same paragraph in line 5 "median follow up of 24 months". This should be 
followed by a period, not coma with the sentence that has to follow be written as " the prognostic 
value of NK cells on long term survival still need to be investigated in future stu dies". In the 
same paragraph line 7 it should be written as" which have different antitumor activity, not 'has'. 
In line 9, it should be "future studies".  
 
11) Under conclusion section, in line 3, "could increase (not increased) the prognostic valve". In 
the same line, the following sentence should be corrected as follows "However, future studies are 
needed in order to verify our results"  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work includ e 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 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:  
 
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, f ees, funding, or salary 
from an organisation that may in any way gain or lose financially from the 
publi cation of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat 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 curr ently 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.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named rep ort 
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 understa nd that any comments 
which I do not wish to be included in my named report can be in cluded 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: 14 Nov 2019  
 
Reviewer: Saikiran Raghavapuram  
 
Reviewer's report:  
 
Authors have written about the survival effect of NK cells in patients with colon cancer. It's a 
retrospective study. The a rticle may need following corrections:  
 
1) On page 5 under the section of data collection, "were extracted" was used twice. I suggest 
removing the "were extracted" from the first sentence and just write as:" The clinicopathological 
features of CRC includi ng" . In the same paragraph, it is better to expand the abbreviations of 
CRP,hsCRP, NLR, PLR, CRP/ALB ratio in the paragraph itself in addition to the expansion of 
these under the table 2 as done by the authors.  
 
2) It is noted that the 447 patient charts from January 2015 to Oct 2018 were considered. But 
how many of these patients were seen close to Oct 2018 was not mentioned. This matters 
because if there are large number of patients that are seen close to end of study period that is Oct 
2018, the results  of their follow up would be skewed.  
 
3) In the first paragraph of results section under "clinic characteristics of study population", 
second line should say 224 colon cancer (not adenoma) and 224 rectal cancer ( not rectal 
adenoma). Nomenclature should change from 'adenoma' to 'cancer' and al so appropriate space 
should be given. Also, its "clinic characteristics of study population " not populations as 
population is ltself pleural.  
  
4) Among 60 patients who died, it would be useful to know how many of them were diagnosed 
with colon cancer yea r wise (how many of those were diagnosed in 2015, 2016,2017 and in 
2018). Also a sub group analysis of NK cells in those 60 compared to live 387 patients with their 
year of diagnosis would be more informative.  
 
5) Any explanation from the authors as to w hy the NK cells percentage does not correlate with 
survival time in patients with rectal cancer when one of the study that is quoted by Coyle etal 
actually found improved survival in rectal cancer patients. (Natural killer -like signature observed 
post ther apy in locally advanced rectal cancer is a determinant of pathological response and 
improved survival.Alderdice M1, Dunne PD2, Cole AJ2,3, O'Reilly PG2, McArt DG1, Bingham 
V1, Fuchs MA1, McQuaid S1, Loughrey MB2,4, Murray GI5, Samuel LM6, Lawler M2, Wilson  
RH2,3, Salto -Tellez M1,2,4, Coyle VM2,3).  
 
6) In the paragraph under the heading "Association of NK cell with the clinicopathological 
features" the following line "The association of NK cells with patient age, gender ...were 
analysed (not analysis).  
7) In first sentence of page 9, it should be "joined", not "jointed".  
 
8) In page 9 discussion section, line 7 instead of "patients, they" write as "patients and found". 
Also in line 9, "inconsistent resulted also reported" should be followed by a period, not comma.  
 
9) In page 10, third paragraph line in placed of "increased prognostic value" it should be "can 
increase the prognostic value".  
 
10) In page 11, line 3, it should be " this study was a retrospective design which may lead to 
selection bias". In the  same paragraph in line 5 "median follow up of 24 months". This should be 
followed by a period, not coma with the sentence that has to follow be written as " the prognostic 
value of NK cells on long term survival still need to be investigated in future stu dies". In the 
same paragraph line 7 it should be written as" which have different antitumor activity, not 'has'. 
In line 9, it should be "future studies".  
 
11) Under conclusion section, in line 3, "could increase (not increased) the prognostic valve". In 
the same line, the following sentence should be corrected as follows "However, future studies are 
needed in order to verify our results"  
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work includ e 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 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:  
 
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, f ees, funding, or salary 
from an organisation that may in any way gain or lose financially from the 
publi cation of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat 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 curr ently 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.  
 
I agree to the open peer review policy of the journal. I understan d that my name will be included 
on my report to the authors and, if the manuscript is accepted for publication, my named rep ort 
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 understa nd that any comments 
which I do not wish to be included in my named report can be in cluded as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant