Review History


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Summary

  • The initial submission of this article was received on April 13th, 2023 and was peer-reviewed by 2 reviewers and the Academic Editor.
  • The Academic Editor made their initial decision on May 14th, 2023.
  • The first revision was submitted on June 28th, 2023 and was reviewed by 2 reviewers and the Academic Editor.
  • The article was Accepted by the Academic Editor on July 26th, 2023.

Version 0.2 (accepted)

· Jul 26, 2023 · Academic Editor

Accept

I suggest authors to go through the latest comments from the reviewers and address them in the final version of the manuscript.

[# PeerJ Staff Note - this decision was reviewed and approved by Paula Soares, a PeerJ Section Editor covering this Section #]

**PeerJ Staff Note:** Although the Academic and Section Editors are happy to accept your article as being scientifically sound, a final check of the manuscript shows that it would benefit from further editing. Therefore, please identify necessary edits and address these while in proof stage.

·

Basic reporting

Check additional comments

Experimental design

Check additional comments

Validity of the findings

Check additional comments

Additional comments

The authors have addressed most of my comments. There are several minor comments that need to be addressed:
1) Line 128, "Only those clinical variables that passed ..", if authors want to express "only significant variables in both models are selected", please make it clear. "pass" here is still confusing.
2) Figure 6 caption, Cox logistic regression analyses, please remove "logistic".

·

Basic reporting

Correct formal English has been revised as previously indicated.
Sufficient review of literature was presented to provide a clear the background.
Problem and objectives were described clearly.
Article manifests professional structure of a typical research article furnished with the relevant results supported with the relevant data (tables, figures and supplementary data regarding databases and the corresponding bioinformatic software used).

Experimental design

This research article presents original and primary research which lie within the aims and scope of the Peerj Journal.

Research question is well defined and gap in the existing knowledge filled with by the current research clearly reported.

Ethical and technical standards were adopted to perform the research.

Methods described by the authors are quite sufficient and within the scope and limits of the planned research.

Risk-score model regarding r the classification of cervical cancer patients into high-risk and low-risk groups was constructed and validated very well.

Validity of the findings

The results reported by the authors are novel and meaningful.
All necessary data pertaining to results have been provided.
The results presented are created using sufficient statistical and bioinformatic analyses
Conclusions are well stated and are linked to the original research performed.
The conclusions are in line with the original research question and results.
miRNA-based risk score model and the integrated monogram were provided
for academic and not-for-profit use which is appreciated.

Additional comments

This article has already been submitted to Medrxiv.
After re-reviewing, I recommend it for publication in PeerJ.

Version 0.1 (original submission)

· May 14, 2023 · Academic Editor

Major Revisions

I suggest authors go through the comments from both reviewers and address them in the revised version of the manuscript

[# PeerJ Staff Note: Please ensure that all review and editorial comments are addressed in a response letter and any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate. #]

[# PeerJ Staff Note: The review process has identified that the English language must be improved. PeerJ can provide language editing services - please contact us at copyediting@peerj.com for pricing (be sure to provide your manuscript number and title) #]

·

Basic reporting

For the table and figure caption, please put all the conclusive sentences in the Results section instead of the caption part. For example, Figure 2, “All the prognostic DEmiRS were upregulated, but none were an outlier DEmiR, …”; Figure 6, “Surprisingly, neither the ….”.

Experimental design

The authors should include the version information for all the software and R packages in this work.

Validity of the findings

In this study, the authors utilized the TCGA dataset, which comprised 312 samples, including 309 cervical cancer tissues and only 3 matched normal tissues. Since the sample size in the normal group is relatively small, it raises concerns regarding the generalizability of the results to new patients based on this data. Is it possible for the authors to consider including more normal samples in their study?

Additional comments

In this work, the authors aim to apply a cascade of filters in miRNA -omics data to find the most predictive miRNA biomarkers. The workflow implemented in this work is a combination of multiple existing methods including DE analysis, cox model, feature selection, etc. The authors identified hsa-miR-625-5p, hs-miR-95-3p, and hsa-miR-330-3p to be the three most predictive miRNA biomarkers for predicting the survival of cervical cancer patients.
Reviewer feels that the manuscript may have been well executed at the lab level, however, the imbalanced sample size in case/control group may lead to results that are difficult to generalize to new data. In addition, there are some remarks from my side that should be addressed by the authors before the manuscript should be published.

Comments:
Line 76, “… histologic grade, vital status and were retained”, it looks like that there is one variable missing.
Line 77, “… in expression across samples (expression σ < 1)”, what is the sigma here? Is it a measure to indicate the difference between case and control? Please make it clear.
Line 82, “… using the limma package in R [10]. The workflow was essentially adapted from earlier protocols developed in our lab [11].” I am little bit confused here, the limma paper was published in 2015, the authors’ previous work was published in 2019. How could authors state that “the workflow was essentially adapted from earlier protocols developed in our lab”. Please explain it and make it clear. If I misunderstood, please let me know.
Line “Univariate Cox models …”, to fit the cox model, the survival data is needed, in the previous text, the authors didn’t mention where they get the survival data, please add it in the main text.
Line 93, “Univariate Cox models … and only DEmiRs with p-value < 0.05 were filtered for further analysis.” Usually, for multiple tests, p-value adjustments should be implemented. Can the authors clarify whether they performed p-value adjustments and provide an explanation for their decision not to do so, or consider updating their methodology to include such adjustments?
Line 101, “…a stepwise multivariate Cox logistic regression…”, what do authors mean the cox logistic regression here? For cox model, the response is survival time and event indicator, for logistic model, the response is binary. I have never heard about cox logistic model. Please check and update it in the manuscript.
Line 105, “… the survival risk of each patient. It is given by the exponent in the multivariate Cox model.” What do you mean “the exponent in the multivariate Cox model”? Please explain the “exponent” you mention here.
Line 118, “Both univariate and multivariate Cox regression analyses were performed …” Do authors implement the regression with only covariates or also with selected miRNAs included? It makes more sense to me if you include both miRNAs and covariates in the model.
Line 120, “Only those clinical variables that survived…” What do authors mean “survived” here, please make it clear.
Line 182, “(p < 0.032)”, change “<” to “=”.

·

Basic reporting

Though professional English was used a few sentences need to be improved to ensure clarity and understanding your text by a broader readership. For example, language could be improved
in lines 76, 77, 78, 82, 83, 127, 128, and 134. Authors are suggested to revise/rephrase the indicated sentences.
Sufficient review of literature was presented to provide a clear the background.
Problem and objectives were described clearly.
Article manifests professional structure of a typical research article furnished with the relevant results supported with the relevant data (tables, figures and supplementary data regarding databases and the corresponding bioinformatic software used).

Experimental design

This research article presents original and primary research which lie within the aims and scope of the Peerj Journal.

Research question is well defined and gap in the existing knowledge filled with by the current research clearly reported.

Ethical and technical standards were adopted to perform the research.

Methods described by the authors are quite sufficient and within the scope and limits of the planned research.

Risk-score model regarding r the classification of cervical cancer patients into high-risk and low-risk groups was constructed and validated very well.

Validity of the findings

The results reported by the authors are novel and meaningful.
All necessary data pertaining to results have been provided.
The results presented are created using sufficient statistical and bioinformatic analyses
Conclusions are well stated and are linked to the original research performed.
The conclusions are in line with the original research question and results.
miRNA-based risk score model and the integrated monogram were provided
for academic and not-for-proft use which is appreciated.

Additional comments

When screened for % similarity index (plagiarism), it was found that this article has already been submitted to Medrxiv therefore, it showed 88% matches to the same submission which can be neglected for estimating plagiarism. However, editors are suggested to ensure the accepted range of plagiarism before final acceptance and publication.

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