PONE-D-24-06933Quantitative proteomics analysis reveals possible anticancer mechanisms of 5'-deoxy-5'-methylthioadenosine in cholangiocarcinoma cellsPLOS ONE

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"This research was supported by the National Science, Research and Innovation Fund (NSRF) and Prince of Songkla University (Ref. No. SCI6701024S) to Sumalee Obchoei. Kankamol Kerdkumthong was supported by a Prince of Songkla University-Ph.D. Scholarship (PSU_PHD2561-001). Phonprapavee Tantimetta was supported by a Prince of Songkla University-Ph.D. Scholarship (PSU_PHD2565-002)."

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Comments to the Author

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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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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: I have carefully reviewed your manuscript on the anticancer activity of 5'-deoxy-5'-methylthioadenosine (MTA) in cholangiocarcinoma cell lines, focusing on the proteomic insights provided. Strengths of your paper include the thorough exploration of MTA's impact on cell viability, apoptosis, migration, and invasion in cholangiocarcinoma cell lines. To further enhance the robustness and impact of your study, I recommend considering the following points:

1.The expression of MTAP in MMNK and KKU-213A-B cell lines should be evaluated, as never has been published before. Regarding to this point, the reference you cite about the establishment of these cell lines is wrong (number #12). The correct one is the following: PMID: 32207095

2. You need to validate by western blot analysis the most representative genes associated with the pathways and processes identified in the proteomic study particularly concerning the biological effects of MTA on apoptosis, growth, viability, invasion, and migration of the cells you show. This validation approach will not only strengthen the findings of the study but also offer a deeper understanding of how these genes contribute to the cellular responses induced by MTA treatment.

3. Why did you choose KKU-213A for proteomic analysis? Which are the main differences between KKU-213A and KKU-213B cell lines?

4. The results in gemcitabine-resistant cell line experiments do not add any value to the work if they are not properly validated or discussed, so they need to be better discussed or otherwise removed from the manuscript.

Minor concerns:

1. Legend of figure 2: *p<0.05…etc statistical significances is it supposed to be between MTA and control-treated cells at every time-points? Please, write it properly.

2. The reference about gemcitabine resistant cells (Kerdkumthong et al, 2023) is not listed in the Bibliography section. Please, include it.

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Reviewer #1: No

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Quantitative proteomics analysis reveals possible anticancer mechanisms of 5'-deoxy-5'-methylthioadenosine in cholangiocarcinoma cells

PONE-D-24-06933R1

Dear Dr. Obchoei,

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,

Matias A Avila, Ph.D.

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

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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: 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: I am pleased to inform you that your manuscript has met all the requirements and addressed the reviewers' comments satisfactorily.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

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