PONE-D-22-03455Disease progression role as well as the diagnostic and prognostic value of MicroRNA-21 in patients with cervical cancer:  A Systematic Review and Meta-AnalysisPLOS ONE

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-https://obgyn.onlinelibrary.wiley.com/doi/10.1002/ijgo.13879

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Reviewers' comments:

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Comments to the Author

1. 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: 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 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: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. 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: 1) RT-PCR

Almost all the articles included in the meta-analysis had mirna-21 assayed with RT-PCR. Why weren’t efforts made to include miRNA studies were the value of mirna-21 assayed via other platforms such as sequencing. I believe adding such studies would not increase the sample size of the study but will also help categorizing a consistent effect of mirna-21 in predicting disease status but also across other assays.

2) Heterogeneity with AUC

It is not surprising to see the heterogeneity for AUC values across the included studies. The values of mirna-21 will highly deviates based on clinical predictors as exposure to HPV, age at diagnosis, family history, and other comorbidities, etc. The authors should explicitly summarize these patient characteristics.

In all the presented studies was mirna-21 the only predictor used? Did any study use any other mirna along with mirna-21 for the analysis?

3) Outliers

A study reported by Aftab et.al has shown two AUC’s > 95%. This study possibly has a class bias, and the data is skewed towards one class. It will be interesting to see if the analysis is repeated by dropping these two studies and the meta-analysis is redone.

4) Miscellaneous

a) Please change microR-21 to microRNA-21 at all instances required.

b) I recommend including more articles by expanding the publication dates. The current window of ~2 months is very limited to perform a metanalysis.

c) Would it be possible to include studies that has not reported the AUC? The authors can include effect size as a metric in the analysis and add a separate analysis.

Reviewer #2: Topic is interesting and study is good. There are few revisions suggested to the authors.

1. Results about qualitative analysis (n =40, disease progression); (n=6, prognosis) needs to be evident for this a table for charesteritics of included studies may be given as a supplementary table.

2.Results for Egger's test and Begg's test not given.

3. Justification for using various different statisticak packages for metaanalyis (MedCalc- version 20.023, Review Manager 5.3, and Stata 11.0)

4 Abbreviation AUROC and AUC define when appeared first time in text of paper.

5.Though it is given that data extraction done by two authors but no mention about literature search done by whom/ How many authors independently.

6.Method section please rewrite the scentence"The studies have been retrieved from November 26, 2021 to January 18, 2022 and all the 162 articles accessed until January 18, 2022" it is confusing and appears that these are the cut off dates for literature search period.

7.Table 2 not clear : in prisma chart no. of included studies is given 7 in table it is given as 10 out of which two studies with * mark excluded so number comes is 9 . Please cross check no of studies include in metaanalyis.

8. Table 2 Again this table is regarding the characteristics of included studies in the systematic review and meta-analysis and authors included two studies that are not included in metaanalyis then why these studies included in table 2 . Either delete or give the justification in foot note. Expansion of AUROC also needs to be given in foot note.

9. In figure 4 for metaanalysis of sensitivity and specificity what model used (fixed or random ) not give. In foot note expand the abbriviations used in figure 4.

10 how the quality assessment done for studies included in qualitative analysis.

11. Contribution of each author needs to be given and not just one author.

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Reviewer #1: Yes: Hrishikesh Lokhande

Reviewer #2: No

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Disease progression role as well as the diagnostic and prognostic value of MicroRNA-21 in patients with cervical cancer:  A Systematic Review and Meta-Analysis

PONE-D-22-03455R1

Dear Dr. Alemu Gebrie,

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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Kind regards,

Khushboo Irshad, Ph.D.

Academic Editor

PLOS ONE

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 #2: 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 #2: Yes

**********

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

Reviewer #2: Yes

**********

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 #2: 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 #2: 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 #2: All the issues are addressed successfully, only a minor comment/suggestion to give individual authors contributions as acknowledgement is to acknowledge work of others and not the authors.

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Reviewer #2: No