Reviewer ’s report  
 
Title: miR-363-5p as potential prognostic marker for hepatocellular carcinoma indicated by  
weighted co -expression network analysis of miRNAs and mRNA  
 
Version: 0 Date: 21 Feb 2017  
 
Reviewer: Uma Chandran  
 
Reviewer's report:  
 
This manuscript describes the potential enrichment of miRs in Hepatacellular Carcinoma using 
TCGA data sets and published WGCNA methods.  
 
This is a largely descriptive study which does not develop new methods and alg orithms but used 
published tools.  
 
 
Major comments:  
 
1. The writing although satisfactory needs to be edited and spell checked more thoroughly.  
 
 
 
2. Were any modificationsm made of the WGCNA methods or the methods used largely as 
described in the original pa per? 
 
 
 
3. The use of descriptive colors in the module analysis is very confusing. The figures have a 
lot of colors, difficult to understand what the colors contribute. Is this the way it is 
described in the original paper? Would have sufficed to say that a " certain number of 
modules were founds of which a few were further analysis". Repeating the color scheme 
as identifiers does not add to the manuscript and only makes it very confusing to follow.  
 
 
 
4. The GO analysis of the modules is not particularly importan t because this analysis is 
largeley descriptive and doesn not add to understand the mechanism of HCC. For 
example, the GO terms are rather vague and whether they are of signficance to HCC is 
not discussed.  
 
 
5. Of the miRs modules are that are considered to be significantly associated with the tumor 
stage and age, why is only miR 363 -5p chosen for further analysis. Each of the miR 
modules must have consisted of dozens of miRs, why was only chosen? Were the others 
not found to significantly correlated with cli nical features?  
 
 
 
6. The median FPKM of the above miR is only 4.6. This is rather low. How many samples 
were above and below this median and what is the range of expression? Were there any 
filters applied for the miR analyis as was done for mRNA analysis?  
 
 
 
7. What was the p value of the Kaplan Meier analysis adjusted for false discvovery? What 
was the adjusted p value  
 
 
 
8. The most significant flaw of this manuscript is that it is descriptive, using public datasets 
and publicly available tools, does not add an y methods to the literature and does not 
include further validation of the hypothesis that miR 363 -5p is important in HCC.  
 
 
 
 
 
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 r equired 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.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
addi tional 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 manuscript:  
 
Needs some language corrections before being published  
 
 
 
 
Declaration of competing interests  
Please comp lete 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 t his 
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, write 'I declare that I have no competing interests' 
below.  If you r reply is yes to any, please give details below.  
 
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 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 a n 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: miR-363-5p as potential prognostic marker for hepatocellular carcinoma indicated by  
weighted co -expression network analysis of miRNAs and mRNA  
 
Version: 0 Date: 21 Feb 2017  
 
Reviewer: Uma Chandran  
 
Reviewer's report:  
 
This manuscript describes the potential enrichment of miRs in Hepatacellular Carcinoma using 
TCGA data sets and published WGCNA methods.  
 
This is a largely descriptive study which does not develop new methods and alg orithms but used 
published tools.  
 
 
Major comments:  
 
1. The writing although satisfactory needs to be edited and spell checked more thoroughly.  
 
 
 
2. Were any modificationsm made of the WGCNA methods or the methods used largely as 
described in the original pa per? 
 
 
 
3. The use of descriptive colors in the module analysis is very confusing. The figures have a 
lot of colors, difficult to understand what the colors contribute. Is this the way it is 
described in the original paper? Would have sufficed to say that a " certain number of 
modules were founds of which a few were further analysis". Repeating the color scheme 
as identifiers does not add to the manuscript and only makes it very confusing to follow.  
 
 
 
4. The GO analysis of the modules is not particularly importan t because this analysis is 
largeley descriptive and doesn not add to understand the mechanism of HCC. For 
example, the GO terms are rather vague and whether they are of signficance to HCC is 
not discussed.  
 
 
5. Of the miRs modules are that are considered to be significantly associated with the tumor 
stage and age, why is only miR 363 -5p chosen for further analysis. Each of the miR 
modules must have consisted of dozens of miRs, why was only chosen? Were the others 
not found to significantly correlated with cli nical features?  
 
 
 
6. The median FPKM of the above miR is only 4.6. This is rather low. How many samples 
were above and below this median and what is the range of expression? Were there any 
filters applied for the miR analyis as was done for mRNA analysis?  
 
 
 
7. What was the p value of the Kaplan Meier analysis adjusted for false discvovery? What 
was the adjusted p value  
 
 
 
8. The most significant flaw of this manuscript is that it is descriptive, using public datasets 
and publicly available tools, does not add an y methods to the literature and does not 
include further validation of the hypothesis that miR 363 -5p is important in HCC.  
 
 
 
 
 
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 r equired 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.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
addi tional 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 manuscript:  
 
Needs some language corrections before being published  
 
 
 
 
Declaration of competing interests  
Please comp lete 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 t his 
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, write 'I declare that I have no competing interests' 
below.  If you r reply is yes to any, please give details below.  
 
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 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 a n 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: miR-363-5p as potential prognostic marker for hepatocellular carcinoma indicated by  
weighted co -expression network analysis of miRNAs and mRNA  
 
Version: 0 Date: 21 Feb 2017  
 
Reviewer: Uma Chandran  
 
Reviewer's report:  
 
This manuscript describes the potential enrichment of miRs in Hepatacellular Carcinoma using 
TCGA data sets and published WGCNA methods.  
 
This is a largely descriptive study which does not develop new methods and alg orithms but used 
published tools.  
 
 
Major comments:  
 
1. The writing although satisfactory needs to be edited and spell checked more thoroughly.  
 
 
 
2. Were any modificationsm made of the WGCNA methods or the methods used largely as 
described in the original pa per? 
 
 
 
3. The use of descriptive colors in the module analysis is very confusing. The figures have a 
lot of colors, difficult to understand what the colors contribute. Is this the way it is 
described in the original paper? Would have sufficed to say that a " certain number of 
modules were founds of which a few were further analysis". Repeating the color scheme 
as identifiers does not add to the manuscript and only makes it very confusing to follow.  
 
 
 
4. The GO analysis of the modules is not particularly importan t because this analysis is 
largeley descriptive and doesn not add to understand the mechanism of HCC. For 
example, the GO terms are rather vague and whether they are of signficance to HCC is 
not discussed.  
 
 
5. Of the miRs modules are that are considered to be significantly associated with the tumor 
stage and age, why is only miR 363 -5p chosen for further analysis. Each of the miR 
modules must have consisted of dozens of miRs, why was only chosen? Were the others 
not found to significantly correlated with cli nical features?  
 
 
 
6. The median FPKM of the above miR is only 4.6. This is rather low. How many samples 
were above and below this median and what is the range of expression? Were there any 
filters applied for the miR analyis as was done for mRNA analysis?  
 
 
 
7. What was the p value of the Kaplan Meier analysis adjusted for false discvovery? What 
was the adjusted p value  
 
 
 
8. The most significant flaw of this manuscript is that it is descriptive, using public datasets 
and publicly available tools, does not add an y methods to the literature and does not 
include further validation of the hypothesis that miR 363 -5p is important in HCC.  
 
 
 
 
 
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 r equired 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.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
addi tional 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 manuscript:  
 
Needs some language corrections before being published  
 
 
 
 
Declaration of competing interests  
Please comp lete 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 t his 
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, write 'I declare that I have no competing interests' 
below.  If you r reply is yes to any, please give details below.  
 
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 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 a n 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