Reviewer’ s report
Title: Transcriptomic analysis on the effects of melatonin in gastrointestinal carcinomas
Version: 0Date: 08 Apr 2020
Reviewer: Peter Schemmer
Reviewer's report:
Lu Ao et al. tried to give in their manuscript entitled "Transcriptomic analysis on the effects of
melatonin in gastrointestinal carcinomas" to give a comprehensive understanding of the effects ofmelatonin on gastrointestinal carcinomas. The topic is hot because there is a lot of research goingon in order to minimize chemoresistance and side effects of chemotherapeutics on the one handand increase the success of chemotherapy.The experiments were performed using gastric cancer cell line HGC-27 and colorectaladenocarcinoma cell line HCT-8 cells as well as the human hepatocellular carcinoma cell linesHepG2 and Huh-7.Interestingly, the authors described 4 common pathways enriched by those DEGs which wereupregulated in three cancers but downregulated in all four cell lines treated by melatonin,including ribosome biogenesis in eukaryotes, RNA transport, spliceosome and cell cycle signalingpathways. These results suggest that melatonin might exert antitumor effects through thesepathways. The authors investigated the effects of melatonin on chemoresistance and could showthat Melatonin exerts the effects of pro-apoptosis and anti-proliferation on gastrointestinalcarcinoma cel llines, and might increase the sensitivity of 5-FU in gastric cancer and colorectalcancer.The authors are aware of the fact that this study is performed under "laboratory conditions" and in
vivo experiments should be performed in order to get more detailed insights in the processes
caused by the administration of melatonin.
The authors should mention in their introduction different additives and substances which are
under investigation in chemotherapeutic regimens such as glycine (Dietary glycine decreases bothtumor volume and vascularization in a combined colorectal liver metastasis and chemotherapymodel. Maneikyte J, Bausys A, Leber B, Horvath A, Feldbacher N, Hoefler G, Strupas K, StieglerP, Schemmer P.), and broccoli sprout (Broccoli sprout supplementation in patients with advancedpancreatic cancer is difficult despite positive effects-results from the POUDER pilot study.Lozanovski VJ, Polychronidis G, Gross W, Gharabaghi N, Mehrabi A, Hackert T, Schemmer P,Herr I.Invest New Drugs. 2019 Jun 27).
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.
YesAre 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 furtherassessment in your comments to the editors.
I recommend additional statistical reviewQuality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being publishedDeclaration 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 thismanuscript, 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 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 report to the authors and, if the manuscript is accepted for publication, my named reportincluding 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 CommonsCC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any commentswhich I do not wish to be included in my named report can be included as confidential commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
Reviewer’ s report
Title: Transcriptomic analysis on the effects of melatonin in gastrointestinal carcinomas
Version: 0Date: 08 Apr 2020
Reviewer: Peter Schemmer
Reviewer's report:
Lu Ao et al. tried to give in their manuscript entitled "Transcriptomic analysis on the effects of
melatonin in gastrointestinal carcinomas" to give a comprehensive understanding of the effects ofmelatonin on gastrointestinal carcinomas. The topic is hot because there is a lot of research goingon in order to minimize chemoresistance and side effects of chemotherapeutics on the one handand increase the success of chemotherapy.The experiments were performed using gastric cancer cell line HGC-27 and colorectaladenocarcinoma cell line HCT-8 cells as well as the human hepatocellular carcinoma cell linesHepG2 and Huh-7.Interestingly, the authors described 4 common pathways enriched by those DEGs which wereupregulated in three cancers but downregulated in all four cell lines treated by melatonin,including ribosome biogenesis in eukaryotes, RNA transport, spliceosome and cell cycle signalingpathways. These results suggest that melatonin might exert antitumor effects through thesepathways. The authors investigated the effects of melatonin on chemoresistance and could showthat Melatonin exerts the effects of pro-apoptosis and anti-proliferation on gastrointestinalcarcinoma cel llines, and might increase the sensitivity of 5-FU in gastric cancer and colorectalcancer.The authors are aware of the fact that this study is performed under "laboratory conditions" and in
vivo experiments should be performed in order to get more detailed insights in the processes
caused by the administration of melatonin.
The authors should mention in their introduction different additives and substances which are
under investigation in chemotherapeutic regimens such as glycine (Dietary glycine decreases bothtumor volume and vascularization in a combined colorectal liver metastasis and chemotherapymodel. Maneikyte J, Bausys A, Leber B, Horvath A, Feldbacher N, Hoefler G, Strupas K, StieglerP, Schemmer P.), and broccoli sprout (Broccoli sprout supplementation in patients with advancedpancreatic cancer is difficult despite positive effects-results from the POUDER pilot study.Lozanovski VJ, Polychronidis G, Gross W, Gharabaghi N, Mehrabi A, Hackert T, Schemmer P,Herr I.Invest New Drugs. 2019 Jun 27).
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.
YesAre 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 furtherassessment in your comments to the editors.
I recommend additional statistical reviewQuality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being publishedDeclaration 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 thismanuscript, 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 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 report to the authors and, if the manuscript is accepted for publication, my named reportincluding 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 CommonsCC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any commentswhich I do not wish to be included in my named report can be included as confidential commentsto 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: Transcriptomic analysis on the effects of melatonin in gastrointestinal carcinomas
Version: 0Date: 08 Apr 2020
Reviewer: Peter Schemmer
Reviewer's report:
Lu Ao et al. tried to give in their manuscript entitled "Transcriptomic analysis on the effects of
melatonin in gastrointestinal carcinomas" to give a comprehensive understanding of the effects ofmelatonin on gastrointestinal carcinomas. The topic is hot because there is a lot of research goingon in order to minimize chemoresistance and side effects of chemotherapeutics on the one handand increase the success of chemotherapy.The experiments were performed using gastric cancer cell line HGC-27 and colorectaladenocarcinoma cell line HCT-8 cells as well as the human hepatocellular carcinoma cell linesHepG2 and Huh-7.Interestingly, the authors described 4 common pathways enriched by those DEGs which wereupregulated in three cancers but downregulated in all four cell lines treated by melatonin,including ribosome biogenesis in eukaryotes, RNA transport, spliceosome and cell cycle signalingpathways. These results suggest that melatonin might exert antitumor effects through thesepathways. The authors investigated the effects of melatonin on chemoresistance and could showthat Melatonin exerts the effects of pro-apoptosis and anti-proliferation on gastrointestinalcarcinoma cel llines, and might increase the sensitivity of 5-FU in gastric cancer and colorectalcancer.The authors are aware of the fact that this study is performed under "laboratory conditions" and in
vivo experiments should be performed in order to get more detailed insights in the processes
caused by the administration of melatonin.
The authors should mention in their introduction different additives and substances which are
under investigation in chemotherapeutic regimens such as glycine (Dietary glycine decreases bothtumor volume and vascularization in a combined colorectal liver metastasis and chemotherapymodel. Maneikyte J, Bausys A, Leber B, Horvath A, Feldbacher N, Hoefler G, Strupas K, StieglerP, Schemmer P.), and broccoli sprout (Broccoli sprout supplementation in patients with advancedpancreatic cancer is difficult despite positive effects-results from the POUDER pilot study.Lozanovski VJ, Polychronidis G, Gross W, Gharabaghi N, Mehrabi A, Hackert T, Schemmer P,Herr I.Invest New Drugs. 2019 Jun 27).
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.
YesAre 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 furtherassessment in your comments to the editors.
I recommend additional statistical reviewQuality of written English
Please indicate the quality of language in the manuscript:
Needs some language corrections before being publishedDeclaration 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 thismanuscript, 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 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 report to the authors and, if the manuscript is accepted for publication, my named reportincluding 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 CommonsCC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any commentswhich I do not wish to be included in my named report can be included as confidential commentsto the editors, which will not be published.
I agree to the open peer review policy of the journal
assistant