Reviewer ’s report  
 
Title: Polymorphism in asparagine synthetase is associated with overall survival of 
hepatocellular carcinoma patients  
 
Version: 0 Date: 24 Jan 2017  
 
Reviewer: Zhao -Yan Jiang  
 
Reviewer's report:  
 
This study found rs34050735 in asparagine synthetase associated with hepatocellular carcinoma . 
Major points  
1) The author only mentioned 'computational analysis (AliBaba 2 software), there is an ATF6 
binding site in the promoter region of ASNA gene'  
Is there any reference evidence indicating the regulation of ASNA by ATF6?  
2) What is the hepatiti s virus positive rate of the patients with HCC? The authors only use non -
HBC controls, how about HCV?  
 
3) In the results part, I suggest to add a subtitle for each part of the results for a better reading  
 
4) What is the selection criteria of 2 SNPs of ASNA gene? Any other SNPs in the coding 
sequence? Need to be mentioned or discussed. The authors studied ATF6, why no SNP was 
investigated for this gene? What is the necessity for adding the results of regulation of 
ASNA by ATF6?  
 
5) No data on direct binding of  ATF6 with ASNA was available, the cell study could only 
provide an in -direct relation, CHIP assay might be provided as the authors already aware.  
 
6) Since the authors conclude that 'ASNS and SNP in this gene may associate with HCC and be 
a promising bio -marker of HCC and its survival', a ROC curve should be performed for the 
performance of these SNPs in predicting HCC survival?  
 
7) English language must re -edited.  
Are the methods a ppropriate 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 conclu sions 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 addi tional 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 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, fees, funding, or sa lary 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 public ation 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 de clare 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 included  
on my re port 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 Crea tive 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: Polymorphism in asparagine synthetase is associated with overall survival of 
hepatocellular carcinoma patients  
 
Version: 0 Date: 24 Jan 2017  
 
Reviewer: Zhao -Yan Jiang  
 
Reviewer's report:  
 
This study found rs34050735 in asparagine synthetase associated with hepatocellular carcinoma . 
Major points  
1) The author only mentioned 'computational analysis (AliBaba 2 software), there is an ATF6 
binding site in the promoter region of ASNA gene'  
Is there any reference evidence indicating the regulation of ASNA by ATF6?  
2) What is the hepatiti s virus positive rate of the patients with HCC? The authors only use non -
HBC controls, how about HCV?  
 
3) In the results part, I suggest to add a subtitle for each part of the results for a better reading  
 
4) What is the selection criteria of 2 SNPs of ASNA gene? Any other SNPs in the coding 
sequence? Need to be mentioned or discussed. The authors studied ATF6, why no SNP was 
investigated for this gene? What is the necessity for adding the results of regulation of 
ASNA by ATF6?  
 
5) No data on direct binding of  ATF6 with ASNA was available, the cell study could only 
provide an in -direct relation, CHIP assay might be provided as the authors already aware.  
 
6) Since the authors conclude that 'ASNS and SNP in this gene may associate with HCC and be 
a promising bio -marker of HCC and its survival', a ROC curve should be performed for the 
performance of these SNPs in predicting HCC survival?  
 
7) English language must re -edited.  
Are the methods a ppropriate 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 conclu sions 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 addi tional 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 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, fees, funding, or sa lary 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 public ation 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 de clare 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 included  
on my re port 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 Crea tive 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: Polymorphism in asparagine synthetase is associated with overall survival of 
hepatocellular carcinoma patients  
 
Version: 0 Date: 24 Jan 2017  
 
Reviewer: Zhao -Yan Jiang  
 
Reviewer's report:  
 
This study found rs34050735 in asparagine synthetase associated with hepatocellular carcinoma . 
Major points  
1) The author only mentioned 'computational analysis (AliBaba 2 software), there is an ATF6 
binding site in the promoter region of ASNA gene'  
Is there any reference evidence indicating the regulation of ASNA by ATF6?  
2) What is the hepatiti s virus positive rate of the patients with HCC? The authors only use non -
HBC controls, how about HCV?  
 
3) In the results part, I suggest to add a subtitle for each part of the results for a better reading  
 
4) What is the selection criteria of 2 SNPs of ASNA gene? Any other SNPs in the coding 
sequence? Need to be mentioned or discussed. The authors studied ATF6, why no SNP was 
investigated for this gene? What is the necessity for adding the results of regulation of 
ASNA by ATF6?  
 
5) No data on direct binding of  ATF6 with ASNA was available, the cell study could only 
provide an in -direct relation, CHIP assay might be provided as the authors already aware.  
 
6) Since the authors conclude that 'ASNS and SNP in this gene may associate with HCC and be 
a promising bio -marker of HCC and its survival', a ROC curve should be performed for the 
performance of these SNPs in predicting HCC survival?  
 
7) English language must re -edited.  
Are the methods a ppropriate 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 conclu sions 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 addi tional 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 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, fees, funding, or sa lary 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 public ation 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 de clare 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 included  
on my re port 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 Crea tive 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