PONE-D-21-33504Prognostic value of SPARC in hepatocellular carcinoma: a systematic review and meta-analysisPLOS ONE

Dear Dr. Xia,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. The reviewer(s) recommended major revision to your manuscript. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.Please submit your revised manuscript by 28th February 2022. 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.

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PLOS ONE

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Reviewer Comments to the Author

Reviewer #1: 1&2&3. What are the justifications for the exclusion criteria? For instance, why were similar studies excluded, how was their ‘similarity’ measured, and how did the authors decide which study among similar studies to include?

The ‘Cochrane handbook for systematic reviews of treatments’ (please cite this resource/include it in the references) was used to evaluate publication bias; however, the criteria is different from what is described in the handbook. For instance, what does ‘Other bias’ mean?

The conclusions regarding overall survival and disease-free survival are supported by only 6 and 2 studies, respectively. Due to the small number of studies reviewed and as mentioned in the article, no comprehensive evidence is presented to support the conclusions.

4.A number of sections in this article contain grammatical errors, making it difficult to understand the text. Acronym definitions are not consistent in terms of letter case and whether the acronym is included in parenthesis or the other way around.

The ‘Country’ column in Table 1 seems to be the author’s affiliation, not the country.

Would it be possible to include figures of higher quality? It’s difficult to read the blurred text in figures.

Reviewer #2: The authors are presenting a novel meta-analysis to analyze the predictive significance of SPARC in Hepatocellular Carcinoma patients.

Regardless of the small sample size, the data presented was novel and can be utilized to build future research in trying to pinpoint the association between SPARC and HCC

I do not have any comments for the authors

Reviewer #3: The current manuscript presented a review and meta-analysis to evaluate the reported evidences in scientific domain in order to understand SPARC expression and the prognosis of patients with HCC. The attempt is worth trying but investigators left noticeable methodological flaws in conduct of this meta-analysis/reporting - making results less reliable. Some of Points are mentioned below:

Authors refer present work as Network Meta analysis which is incorrect. (L99)

Authors have not provided Search Strategy Algorithms. The described search strategy in manuscript is of poor quality.

Systematic Review part of manuscript is incomplete, and there is no qualitative synthesis of evidence based on previously reported work.

Authors report that present work included the studies between 2019 and 2020 (L173), however, Table 1 does not comply with that criteria. The manuscript has many such contradictions- seems authors need to verify their data and description text.

Reason for the selection of Random Effects Model is insufficient. Results are insufficiently described which makes difficult to follow the conclusion and discussion part of manuscript.

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PONE-D-21-33504R1Prognostic value of SPARC in hepatocellular carcinoma: a systematic review and meta-analysisPLOS ONE

Dear Dr. Xia,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jun 23 2022 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 you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

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,

Raj Kumar Koiri

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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: (No Response)

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: I have no further comments for the authors.

Reviewer #3: Thank you for providing the additional information in respect of comments. The Queries for the manuscript have been addressed well.

Reviewer #4: In the manuscript titled “Prognostic value of SPARC in hepatocellular carcinoma: a systematic review and meta-analysis” the authors, with the help of data mining evaluated the SPARC expression and posed SPARC as a prognostic marker in hepatocellular carcinoma patients. This is novel in terms of the project plan without any wet laboratory experiments but only with the help of previous work and literature search with certain inclusion and exclusion criteria. The current manuscript is well written with some minor english grammar and typo mistakes. The pointwise comments are as follows:

1. Though the manuscript is well organized but is not easy to understand what is the goal/aim of this study.

2. When there are many other proteins (PIMD 33312759, 34591393, 32439236, 28631558) studied in the HCC why SPARC has been chosen, and what is the rationale behind it?

3. It would be better if the author had defined, what is “overall survival” and what is “disease-free survival”.

4. The entire manuscript is based on data mining and six paper has been selected which is a very small number.

5. The total sample size based upon the 6 papers is 678, according to table 1 (120+89+79+130+60+200 = 678), why and how it is mentioned 698 in line 233 page 13 and line 256 page 14.

6. This manuscript is not a regular research article, many things in the manuscript have to be defined, like “method of group assignment,” (line 177 page 10) and “blinding in the outcome analysis” (line 178 page 10).

7. Instead of presenting in the tabular form, it would be better if all the 6 studies were described with a separate heading including the sample size, methodology used, and putative outcome.

8. Some sentences are incoherent, e.g. “The p53/p21Cip1/Waf1 pathway enhances the effects of radiotherapy and chemotherapy” what does this sentence mean, and how it is correlated with the study?

9. While talking about the limitations of the paper, on page no 14, it is mentioned “other types of biases” in line 260., It is better to describe the “other biases” or just delete this line.

10. What does TNM stand for in line 262, page 14?

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes: Ratnakar Tripathi

[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. Please note that Supporting Information files do not need this step.

Prognostic value of SPARC in hepatocellular carcinoma: a systematic review and meta-analysis

PONE-D-21-33504R2

Dear Dr. Xia,

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.

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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,

Raj Kumar Koiri

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

The authors have satisfactorily answered the reviewers comment and the manuscript can be accepted.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #4: All comments have been addressed

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

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #4: Yes

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

Reviewer #4: Yes

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

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #4: Yes

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

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #4: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #4: In the manuscript titled “Prognostic value of SPARC in hepatocellular carcinoma: a systematic review and meta-analysis” the authors, have answered all the questions and edited according.

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7. PLOS authors have the option to publish the peer review history of their article (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: Ratnakar Tripathi

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