Dear Dr. Murtola,

- language problems should be removed,

- presentation problems must be fixed,

- details of the cohort description should be made clear,

- information about the statistical post-hoc analysis and about data distributions would increase the value of the manuscript,

- internet links used in the references list should be verified and updated ([1] - link is not actual; are Authors sure that such unstable and not reviewed sources should be used as references?).

Please submit your revised manuscript by Feb 27 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Maciej Huk, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf .

2. Thank you for stating in your Funding Statement:

“FinRSPC has been supported by grants from Academy of Finland (grant #260931), Cancer Foundation Finland sr, and Expert Responsibility Area of the Pirkanmaa Hospital District (grant #9V065) (A.A). This study was supported by grant from Cancer Foundation Finland (grant #220055) (T.M). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Please provide an amended statement that declares *all* the funding or sources of support (whether external or internal to your organization) received during this study, as detailed online in our guide for authors at http://journals.plos.org/plosone/s/submit-now.  Please also include the statement “There was no additional external funding received for this study.” in your updated Funding Statement.

Please include your amended Funding Statement within your cover letter. We will change the online submission form on your behalf.

3. We note that you have indicated that there are restrictions to data sharing for this study. For studies involving human research participant data or other sensitive data, we encourage authors to share de-identified or anonymized data. However, when data cannot be publicly shared for ethical reasons, we allow authors to make their data sets available upon request. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

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a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., a Research Ethics Committee or Institutional Review Board, etc.). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of recommended repositories, please see https://journals.plos.org/plosone/s/recommended-repositories. You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible.

Please update your Data Availability statement in the submission form accordingly.

4. In the online submission form, you indicated that your data is available only on request from a third party. Please note that your Data Availability Statement is currently missing [the name of the third party contact or institution / contact details for the third party, such as an email address or a link to where data requests can be made]. Please update your statement with the missing information.

5. Thank you for stating the following in the Acknowledgments Section of your manuscript:

“FinRSPC has been supported by grants from Academy of Finland (grant #260931), Cancer Foundation Finland sr, and Expert Responsibility Area of the Pirkanmaa Hospital District (grant #9V065) (A.A). This study was supported by grant from Cancer Foundation Finland (grant #220055) (T.M). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

We note that you have provided additional information within the Acknowledgements Section that is not currently declared in your Funding Statement. Please note that funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

“FinRSPC has been supported by grants from Academy of Finland (grant #260931), Cancer Foundation Finland sr, and Expert Responsibility Area of the Pirkanmaa Hospital District (grant #9V065) (A.A). This study was supported by grant from Cancer Foundation Finland (grant #220055) (T.M). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

6. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: This text describes the population characteristics of CYP2C9 and VKORC1 genotypes in two study cohorts. The content is clear and logically sound, but there are still some shortcomings and suggestions for improvement:

There is a lack of logical connection between the discussion of prostate cancer risk factors and the coagulation cascade between lines 52 and 53 on page 3. The sections discussing the in vitro studies of warfarin and the current epidemiological situation between lines 60-65 need to be refined for clarity.

Although the methods section mentions that data is sourced from the national cancer registry and hospital records, there is a lack of discussion regarding data quality assessment when describing how to "supplement" cancer diagnosis information. The specific values of the International Normalized Ratio (INR) are not provided, which prevents the classification of patients into good responders and poor responders for analysis. INR is an important indicator for evaluating the anticoagulant effect of warfarin, and the absence of this data may affect the in-depth analysis of warfarin dosage adjustment and efficacy assessment.

The first part of the results mentions differences between genotypes and clinical standards (such as Gleason scores, tumor stages, etc.), but it does not discuss the clinical significance or potential reasons for these results. Please supplement with relevant research evidence.

The results list the hazard ratios (HR) and confidence intervals (CI) for different genotypes, but the clinical significance and biological mechanisms of these results are not discussed, especially regarding why certain genotypes are associated with mortality risk while others are not.

Reviewer #2: ==Language problems==

1. pp 3-4, lines 67-68: Missing article, recommended change: ‘Warfarin targets Vitamin K epOxide Reductase Complex subunit 1 (VKORC1) by inhibiting its activity, an enzyme involved in the vitamin K cycle.’

2. p 5, line 109: Recommended change for improving the readability: ‘The data were accessed for research purposes between January 1, 2022, and October 31, 2024.’

3. p 7, line 140: ‘Only 0.9% of subjects were carrier’ => ‘Only 0.9% of subjects were carriers’

4. Caption of Figure 2: ‘warfaring-metabolizing’ => ‘warfarin-metabolizing’;

5. Caption of Table 4: ‘Data is expressed as hazard ration’ => ‘Data is expressed as hazard ratios’;

==Presentation problems==

1. p 9, lines 188-193: Table 1: Lacking indication that the numbers in parentheses represent the percentages for the row ‘n of men’. Some numbers in the table don’t sum up to the values declared in the caption, e. g. n of men in the screening cohort. Moreover, it is unclear what was intended to be shown regarding the data stratification by SNP type. The description in the caption suggests that the stratification is held in the table, whereas the table itself presents the summed data. It’s recommended to harmonize the description and the tabular data in this context.

2. Figure 1: It is recommended to improve the readability of the cause of death mapping on the graph either by enlarging the font of the geometric figures or by adding color as an auxiliary mapping.

3. Figure 2: The recommendations are similar to those for Figure 1. Apart from that, the figure does not clearly reflect the stratification declared in the caption. It can be deduced from the caption that the second, third, and fourth graphs, as viewed from top to bottom, pertain to warfarin users referenced to the non-users but this information may be overlooked by the reader when scanning the article. Thus, it might be helpful to include this reference in small font individually below the captions of each graph. Additionally, what about the division into two cohorts? Consistently with the caption of Figure 1, I would expect the separate presentation of the results for each of these cohorts. Are they summed up in the Figure 2? If so, it is recommended to indicate this in the caption.

4. Table 2: Adding information to the caption that ‘Ref’ stands for ‘reference group’ would improve the readability of the table. Similarly to the Table 1, it is also recommended to check whether the summations of cases are correct within the cohorts and genotypes.

==Content-related questions and recommendations==

1. p 6, lines 113-114: ‘The study cohort was linked to the national prescription database of the Social Insurance Institution of Finland …’. It is recommended to make this description more precise regarding the cohort or cohorts it refers to. Does this description refer to the screening cohort, the hospital cohort or both? Another fragment which occurs in the lines 143-146 suggests that only screening cohort is concerned but it would be with benefit to readability to mark this information explicitly.

2. p 8, lines 164-165: ‘Interaction was statistically tested including interaction term between warfarin use and SNP genotype into Cox regression model’. Please provide the name of the test used for the evaluation of the interaction term: is it Wald test, Likelihood Ratio Test or other?

3. p 8, lines 177-178: ‘otherwise the distributions of wild type and heterozygous SNP carriers were similar in the two study cohorts’. These frequencies are indeed similar at a glance, but it would be advisable to test the independence of the aforementioned distributions by e.g. Chi-squared test for greater precision and provide the calculated p-value. This remark is more general and refers to other fragments where distributions/frequencies are compared.

RECOMMENDATION: Minor revision

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org

Dear Dr. Murtola,

• language and presentation problems should be removed,
• discussion of results should be extended,
• description of experimental setup (statistical analysis software) need minor updates,
• clinical utility of the study should be clearly expressed.

Please submit your revised manuscript by May 25 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Maciej Huk, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

Reviewer #5: (No Response)

Reviewer #6: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: (No Response)

Reviewer #6: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: (No Response)

Reviewer #6: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #2: No

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: (No Response)

Reviewer #6: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: (No Response)

Reviewer #6: No

**********

Reviewer #2: The authors have addressed the recommendations outlined in my review and implemented the suggested improvements. Therefore, I recommend the acceptance of the submitted paper.

Reviewer #3: All comments have been addressed and I have no further comments to discuss with authors or editors on this manuscript.

Reviewer #4: 1. There are some grammatical, alignments and typographical errors are noted in the manuscript and it should be thoroughly checked and corrected throughout the manuscript.

2. Check the abbreviations throughout the manuscript and introduce the abbreviation when the full word appears the first time in the abstract and the remaining for the text and then use only the abbreviation (For example, Prostate cancer (PCa), CVD, etc.,). Make a word abbreviated in the article that is repeated at least three times in the text, not all words to be abbreviated.

3. In introduction, the authors may cite prevalence or incidence data “Prostate cancer” and it should be in either 2024 or 2025.

4. When referring to SPSS versions beginning from 19, authors should cite ‘IBM SPSS Statistics for Windows, version 21 (IBM Corp., Armonk, N.Y., USA)'.

5. The version of the software used for statistical investigation (Stata) in the present investigation should be given under the heading “Statistical analysis”.

6. The authors may improve the discussion of their results by focusing on the present findings and introducing data from other authors who also worked with the same or other studies with recent references since it is lack of sufficient references.

Reviewer #5: The manuscript titled "SNP genotypes in CYP2C9 and VKORC1 genes do not affect prostate cancer or cancer mortality among warfarin users in Finnish prostate cancer patients" is well-conducted. I read the previous comments from the reviewers. I have some additional comments for improvement:

1- Define abbreviations in their first use and make sure that abbreviated forms are used after the definition.

2- In the discussion, the limitations and strengths should be in a separate heading, just before the conclusions.

3- The discussion section is not comprehensive. Add more data from previous meta-analysis and compare them with your findings.

4- Mention the clinical utility of your findings in the discussion.

5- I found some typos and grammatical errors. A native review is warranted.

Reviewer #6: I think the paper is sound and all comments have been addressed .I think in general the paper is solid and should be published.Besides the results are very usefull for the scientific community involved in this subject

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes:  Dr. A. Vijaya Anand

Reviewer #5: No

Reviewer #6: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org

Dear Dr. Murtola,

In particular:

• grammatical, alignment and typographical errors need to be removed,
• all abbreviations should be defined before their first use.

plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Maciej Huk, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #4: All comments have been addressed

Reviewer #5: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #4: Yes

Reviewer #5: (No Response)

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #4: Yes

Reviewer #5: (No Response)

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #4: Yes

Reviewer #5: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #4: Yes

Reviewer #5: (No Response)

**********

Reviewer #4:  1. There are some grammatical, alignments and typographical errors are noted in the manuscript and it should be thoroughly checked and corrected throughout the manuscript. For example,

• in line number 70, the words “causal” may be as “the causal”;

• in line number 92, “Tampere” as “the Tampere”;

• in line number 151, “Information of” as “Information on”;

• in line number 168, “for death” as “death”;

• in line number 175, “Interaction” as “The interaction”;

• in line number 199, “Gleason” as “a Gleason”;

• in line number 211, “diagnosis” as “a diagnosis”;

• in line number 217, “Similarly,no” as “Similarly, no”;

• in line number 221, “f PCa” as “of PCa”;

• all over the manuscript, “as hazard” as “as a hazard”;

• in line number 6, “anddid” as “and did”;

• in line number 24, “wecannot dretermine” as “we can not determine”;

• in line number 2, “factors..” as “factors.”;

• in line number 17, “International” as “the International”;

• in line number 22, “history” as “a history”;

• in line number 17, “groupss is” as “groups are”;

• in line number 8, “larger” as “a larger”.

2. This suggestion is not carried out properly and it should be rectified. Check the abbreviations throughout the manuscript and introduce the abbreviation when the full word appears the first time in the abstract and the remaining for the text and then use only the abbreviation (For example, Prostate cancer (PCa) and this types of corrections need to be checked all other abbreviations used in the manuscript.

Reviewer #5:  (No Response)

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #4: Yes:  Dr. A. Vijaya Anand

Reviewer #5: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org

SNP genotypes in CYP2C9 and VKORC1 genes do not affect prostate cancer or cancer mortality among warfarin users in Finnish prostate cancer patients

PONE-D-24-50316R3

Dear Dr. Murtola,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Maciej Huk, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #4: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously? -->?>

Reviewer #4: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #4: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #4: Yes

**********

Reviewer #4: 1. This suggestion is not carried out properly and it should be rectified. Check the abbreviations throughout the manuscript and introduce the abbreviation when the full word appears the first time in the abstract and the remaining for the text and then use only the abbreviation (For example, in line number 164, “prostate cancer” should be replaced as “PCa” and this types of corrections need to be checked all other abbreviations used in the manuscript.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy

Reviewer #4: Yes:  Dr. A. Vijaya Anand

**********