Reviewer ’s report  
 
Title: c-Jun N -terminal kinase activation has a prognostic implication and is negatively 
associated with FOXO1 activation in gastric cancer  
 
 
Version: 0 Date: 18 Dec 2015  
 
 
Reviewer: Dan Worthley  
 
 
Reviewer's report:  
 
The study by Choi et al, was designed to address the role of c -Jun N -terminal kinase activation in 
gastric cancer. They used a series of associative studies chiefly immunostaining, some cell line 
work and assessment of survival in their patient cohort. By immunostaining JNK activation was 
inversely associate with gastric cancer stage (1), although is directly associated with cell 
proliferation Ki67 and directly associated with FoXo1. They then trea ted gastric cancer lines 
with a Jnk inhibitor and there was a "substantial decrease in the expression of the inactive form 
of FOXO1," but "total FOXO1 expression was not changed". Luciferase experiments follow and 
they conclude that "it seems that JNK acts  as an inhibitory upstream moleculae of FOXO1". But, 
I was confused why if one inhibited the other that the survival suggested that a loss of both had 
the worse prognosis? If JNK is a good prognostic factor (as suggested in 1) and that JNK inhibits 
FOXO1 t hen wouldn't High JNK and Low FOXO1 show the greatest survival?  
 
I think my confusion relates to the large number of descriptive and inverse associations. The 
authors should, I suggest, at the end of each results section describe how the preceding results 
paragraph adds to their model.  
 
The best data is that of their Seoul National University College of Medicine tumor bank and 
survival data. But, the JNK and FOXO1 results should also be controlled for stage to determine 
if they are independently associated with survival.  
 
Overall I found the study to be a little descriptive, difficult to follow, and lacking significant 
mechanistic insight, but they report on a large patient cohort that will hold interest for some 
readers.  
 
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 ma nuscript:  
 
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,  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 com peting 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 t o the open peer review policy of the journal. I understand that my name will be included  
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: c-Jun N -terminal kinase activation has a prognostic implication and is negatively 
associated with FOXO1 activation in gastric cancer  
 
 
Version: 0 Date: 18 Dec 2015  
 
 
Reviewer: Dan Worthley  
 
 
Reviewer's report:  
 
The study by Choi et al, was designed to address the role of c -Jun N -terminal kinase activation in 
gastric cancer. They used a series of associative studies chiefly immunostaining, some cell line 
work and assessment of survival in their patient cohort. By immunostaining JNK activation was 
inversely associate with gastric cancer stage (1), although is directly associated with cell 
proliferation Ki67 and directly associated with FoXo1. They then trea ted gastric cancer lines 
with a Jnk inhibitor and there was a "substantial decrease in the expression of the inactive form 
of FOXO1," but "total FOXO1 expression was not changed". Luciferase experiments follow and 
they conclude that "it seems that JNK acts  as an inhibitory upstream moleculae of FOXO1". But, 
I was confused why if one inhibited the other that the survival suggested that a loss of both had 
the worse prognosis? If JNK is a good prognostic factor (as suggested in 1) and that JNK inhibits 
FOXO1 t hen wouldn't High JNK and Low FOXO1 show the greatest survival?  
 
I think my confusion relates to the large number of descriptive and inverse associations. The 
authors should, I suggest, at the end of each results section describe how the preceding results 
paragraph adds to their model.  
 
The best data is that of their Seoul National University College of Medicine tumor bank and 
survival data. But, the JNK and FOXO1 results should also be controlled for stage to determine 
if they are independently associated with survival.  
 
Overall I found the study to be a little descriptive, difficult to follow, and lacking significant 
mechanistic insight, but they report on a large patient cohort that will hold interest for some 
readers.  
 
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 ma nuscript:  
 
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,  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 com peting 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 t o the open peer review policy of the journal. I understand that my name will be included  
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: c-Jun N -terminal kinase activation has a prognostic implication and is negatively 
associated with FOXO1 activation in gastric cancer  
 
 
Version: 0 Date: 18 Dec 2015  
 
 
Reviewer: Dan Worthley  
 
 
Reviewer's report:  
 
The study by Choi et al, was designed to address the role of c -Jun N -terminal kinase activation in 
gastric cancer. They used a series of associative studies chiefly immunostaining, some cell line 
work and assessment of survival in their patient cohort. By immunostaining JNK activation was 
inversely associate with gastric cancer stage (1), although is directly associated with cell 
proliferation Ki67 and directly associated with FoXo1. They then trea ted gastric cancer lines 
with a Jnk inhibitor and there was a "substantial decrease in the expression of the inactive form 
of FOXO1," but "total FOXO1 expression was not changed". Luciferase experiments follow and 
they conclude that "it seems that JNK acts  as an inhibitory upstream moleculae of FOXO1". But, 
I was confused why if one inhibited the other that the survival suggested that a loss of both had 
the worse prognosis? If JNK is a good prognostic factor (as suggested in 1) and that JNK inhibits 
FOXO1 t hen wouldn't High JNK and Low FOXO1 show the greatest survival?  
 
I think my confusion relates to the large number of descriptive and inverse associations. The 
authors should, I suggest, at the end of each results section describe how the preceding results 
paragraph adds to their model.  
 
The best data is that of their Seoul National University College of Medicine tumor bank and 
survival data. But, the JNK and FOXO1 results should also be controlled for stage to determine 
if they are independently associated with survival.  
 
Overall I found the study to be a little descriptive, difficult to follow, and lacking significant 
mechanistic insight, but they report on a large patient cohort that will hold interest for some 
readers.  
 
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 ma nuscript:  
 
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,  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 com peting 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 t o the open peer review policy of the journal. I understand that my name will be included  
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