PONE-D-24-25776Gene Expression and Soluble Protein Level of PD-1 and Its Ligands (PD-L1 and PD-L2) in Endometrial CancerPLOS ONE

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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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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

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Reviewer #1:  Present article is so interesting and must be valuable for the patients suffering from uterine endometrial cancer. However, several concerns remain in this article, which suggest as follows:

1) How have you selected the healthy control patients and obtained the endometrial samples? Usually, over 55-years-old females have passed the final menstruation, which make so hard to collect the endometrium. Furthermore, the endometrium from the menopaused female contains relatively less glandular cells compared to pre-menopausal female, which is differ from the breast or lung tissue.

2) As you mentioned in LL321-323, soluble PD-1 and PD-L2 level showed significantly differ age-dependent manner. Actually, these protein level seems associated with age in the ‘case group’, however, as you have not adjusted the age in the ‘control group’, it is impossible compared between two groups.

3) In the process of RNA extraction from the endometrial tissue of control female, have you checked the infiltration of immune cells preliminary? The infiltration of immune cells in the uterine endometrium shows variety during the menstrual cycles in the pre-menopaused female, which may distort your data.

Reviewer #2:  thank you for allowing me to review this paper

The paper investigate the role of PDL1 expression in ec and its role

1-There is a strong correlation between pdl1 expression, TMB, and MMR status. It means that just having MMR status is useful to select patients who fit for ICI. Please comment on this

2- In the introduction of the paper is important to comment on the recent, cumulative data on ICI in first line setting (PMID: 38431043).

3- How about the role of molecular classification

4- How about PDL1 in multiple classsfier endometrial cancer . please discuss this point

5- How about p53 wt and the potential role of selinexor (PMID: 37271639) in patients with and without Pdl1 expression

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Reviewer #1: No

Reviewer #2: No

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Gene Expression and Soluble Protein Level of PD-1 and Its Ligands (PD-L1 and PD-L2) in Endometrial Cancer

PONE-D-24-25776R1

Dear Dr. Chew,

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,

Yasuhiro Miki

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: Yes

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

Reviewer #1: 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 #1: 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 #1: 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 #1: Thank you for correcting your manuscript. I am fully satisfied with all your responses regarding the inquiries.

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If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: No

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