PONE-D-20-00029

Clinicopathological and prognostic significance of caveolin-1 and ATG4C expression in the epithelial ovarian cancer

PLOS ONE

Dear Dr. Chen,

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.

The reviewer of your manuscript indicated that the work was preliminary and recommended that the manuscript be rejected. I am however willing to receive a substantially revised version of the manuscipt if you address comprehensively all the reviewers comments incorporating additional data as requested. Additional mechanistic insight is not necessary.

We would appreciate receiving your revised manuscript by Mar 13 2020 11:59PM. When you are 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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We look forward to receiving your revised manuscript.

Kind regards,

Ivan R. Nabi, Ph.D.

Academic Editor

PLOS ONE

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2. We noticed minor instances of text overlap with the following previous publication(s), which need to be addressed:

(a) https://www.tandfonline.com/doi/full/10.4161/auto.8.2.18351

(b) https://www.spandidos-publications.com/10.3892/etm.2019.7402

(c) https://www.hindawi.com/journals/bmri/2014/462658/

(d) https://www.mdpi.com/2073-4409/8/7/713/htm

The text that needs to be addressed involves the Introduction section.

In your revision please ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

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Reviewers' comments:

Reviewer's Responses to Questions

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

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

Reviewer #1: Yes

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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: The current manuscript by Dr. Chen and colleagues analyzed TCGA data and performed IHC on a TMA in order to determine whether Cav1 and/or ATG4C may correlate with ovarian cancer outcomes. In accordance with a previous study (Wiecher et al), they determined that reduced Cav1 levels associate with a poorer prognosis, particularly in serous cancers. They also determined that ATG4C positively associates with a poorer prognosis. These correlations appeared to occur at the level of mRNA and protein, and also were predictive even after multivariate analyses. Overall, while sound, these results are somewhat confirmatory and rather preliminary. While the TMA is a good resource, much of the analysis could be done online with k-plotter, for example. Hence, a great deal more data would be needed to generate a stand-alone publication.

Specific Comments

• The authors should expand the analysis to include additional sources of data (sequencing as well as tissue). They should also consider correlating Cav1 and ATG4C and confirming IHC findings by performing or analyzing stromal and cancer cells at a single cell resolution.

• The stromal alterations in Cav1 should be confirmed algorithmically in large patient data sets.

• Some mechanistic insight should be provided. How are these genes altered?

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Reviewer #1: No

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PONE-D-20-00029R1

Clinicopathological and prognostic significance of caveolin-1 and ATG4C expression in the epithelial ovarian cancer

PLOS ONE

Dear Dr. Chen,

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.

The authors have addressed the majority of the comments raised previously. The presentation of a significant correlation between CAV1 and Atg4C in tumor and stromal cells in Table 3 is particularly interesting. It would be important therefore to present the clinicopathological features of not only high vs low CAV1 and high vs low ATG4C (Tables 4 and 5) but more particualrly whether the 48 high CAV1 and high ATG4 tumors or low CAV1/low ATG4 stroma present distinctive clinicopathological features.

We would appreciate receiving your revised manuscript by May 02 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Ivan R. Nabi, Ph.D.

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

Clinicopathological and prognostic significance of caveolin-1 and ATG4C expression in the epithelial ovarian cancer

PONE-D-20-00029R2

Dear Dr. Chen,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Ivan R. Nabi, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: