PONE-D-20-39305

Small RNAs as biomarkers to differentiate benign and malign prostate diseases: an alternative to transrectal punch biopsy of the prostate?

PLOS ONE

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Furthermore, could you also indicate whether some statistical links have been pointed out between the various identified miRNA and/or piRNA and the Gleason score?

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PLOS ONE

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Comments to the Author

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

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Reviewer #1: Partly

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

Reviewer #1: Yes

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

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Reviewer #1: Yes

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Reviewer #1: 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: In this paper, authors investigate wether urinary miRNAs and piRNAs can be used as biomarkers to differentiate benign and malign prostate diseases. This should be an alternative to transrectal punch biopsy of the prostate which is a painful and risky procedure.

For that, urine samples from urological patients with BPH (25) or PCa (28) were analysed using Next-Generation Sequencing to detect the expression profile of total and exosomal miRNA/piRNA. Then a differential study was made and 6 miRNAs and 2 piRNAS were statistically validated

In addition, machine-learning algorithms were used to identify a panel of 22 additional miRNAs.

This paper is of interest and well written in its entirety.

The differential study is clear and robust and conclude to a set of potential biomarkers.

However, the machine-learning part is less clear and its interest is not an evidence for me.

MAJOR remarks and questions:

1) In the paper, samples were split randomly into training dataset (18 PCA + 15 BPH) and a test dataset (10 PCA + 10 BPH) for validation. Sizes of dataset were not justified and it is difficult to know the relevance of this choice. It would be necessary to justify this choice.

2) The interest of additionnal biomaker panels found with machine learning method is not evidence for me. This should be clarified and the interest of such a method be clearly shown.

MINOR remarks:

lines 115-116: maybe only use miRNA and not microRNA

line 166: the reading depth -> maybe reading length

line 166: sentence is not really clear

Figure 2: not centered and truncated

Figure 6: problem of legend for PCA and PH

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Reviewer #1: No

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Small RNAs as biomarkers to differentiate benign and malign prostate diseases: an alternative to transrectal punch biopsy of the prostate?

PONE-D-20-39305R1

Dear Dr. Markert,

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,

Jean-Marc A Lobaccaro, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

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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)

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

Reviewer #1: (No Response)

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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)

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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)

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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: My requests are mostly addressed by the authors and I recommend accepting this manuscript in its current form

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Reviewer #1: No