PONE-D-23-02665PAK1 copy number in breast cancer - Associations with proliferation and molecular subtypesPLOS ONE

Dear Dr. Skjervold,

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- https://ntnuopen.ntnu.no/ntnu-xmlui/bitstream/handle/11250/2781262/Valla2021_Article_DTX3CopyNumberIncreaseInBreast.pdf?isAllowed=y&sequence=2

- https://link.springer.com/article/10.1007/s10549-020-06035-0

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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: Yes

Reviewer #2: Yes

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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5. Review Comments to the Author

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Reviewer #1: Dear authors,

I read with interest the article which analyzes the associations between PAK1 CN and proliferation status, molecular subtype, and prognosis in addition to the correlation between CNs of PAK1 and CCND1.

I also think that the molecular targets related to the biological aggressiveness of the tumors could constitute a pharmacological target in the personalization of the treatments.

I recommend this article.

The manuscript clear, relevant for the field and presented in a well-structured manner.

The cited references mostly recent publications (within the last 5 years) are relevant.

The manuscript scientifically sound and is the experimental design appropriate to test the hypothesis.

The manuscript’s results reproducible based on the details given in the methods section (to be implemented).

The figures/tables/images/schemes are appropriate and they properly show the data (easy to interpret and understand).

The statistical analysis or data acquired are appropriate.

The conclusions are consistent with the evidence and arguments presented the ethics statements and data availability statements to ensure they are adequate.

The results interpreted appropriately and are significant. All conclusions are justified and supported by the results and the hypotheses carefully identified. The article written in an appropriate way and the data and analyses presented appropriately.

Reviewer #2: The manuscript was well written, the methodology was sound and the results were highlighted systematically.

However, very few issues need address.

1. Line 8 (page 4): Patients were diagnosed, however it was not stated if patients were categorized into treatment options. We assumed molecular classification played role in treatment options and this will be important in the effect of PAK 1 and Tamoxifen as mentioned in the discussion.

2. Table 3 which should highlight the association of PAK 1 CN with Ki67 and Histological grade is missing

3. Kindly check results for line 15 and 16 on page 7 to make sure that comparisons are made with common denominator

4. Line 2 of page 7 described described age demography, with inconsistent gap, while table 3 assumed to highlight this data is conspicuously missing.

5 The discussions on PAK1 CN and CCND1 was scanty.

Reviewer #3: The manuscript titled PAK1 copy number in breast cancer - Associations with proliferation and molecular subtypes is relevant and corroborated knowledge already known.

Abstract

Aims - change to background or introduction. Define all abbreviations first before use.

Method -This was over summarised. More explanation needed.

Result- Add a comment on how the association was found.

Conclusion- Too long. Let it answer the research question

Body of manuscript

Introduction: adequate. Define all abbreviations before use

Material & methods: Adequate and sound. Check the fish protocol and edit appropriately- Make it flow for ease of understanding.

Result: Adequate but need revisions. 'No clear association....' was used several times. It is unclear what it means.

Pg 7 Line 18-25 and 8:1-3 - revise for clarity; HER2- or HER2 superscript - Stick to one

There is repetition of the entire results in the tables- This makes tables/figures redundant. Just mention important findings in-text.

Table 3 missing

Table 5 and 6 confusing. I will suggest the authors stick to the classification stated in the methodology for copy numbers

Discussion: Generally inadequate. Line 4-9: Repetition of result; not necessary. Line 12-19: This was not given attention in the result.

No discussion on comparison of primary tumor with corresponding lymph node metastasis

Why was the TMA taken from tutor periphery?

Conclusion: Fair.

References: Adequate

General: The manuscript needs grammar and spelling check and discussion should be tailored to the results.

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Reviewer #1: Yes: Paolo Orsaria, MD, PhD;

Reviewer #2: No

Reviewer #3: No

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PAK1 copy number in breast cancer - Associations with proliferation and molecular subtypes

PONE-D-23-02665R1

Dear Dr. Anette,

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.

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Kind regards,

Elingarami Sauli, PhD

Academic Editor

PLOS ONE

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