PONE-D-22-02231Neoplastic signatures: comparative proteomics of canine hepatobiliary neuroendocrine tumors to normal niche tissuePLOS ONE

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” This work was supported in part by NIH grant 1P20GM135000-01A1 and the Louisiana State University, Department of Veterinary Clinical Sciences CORP grant. Proteomic analysis was performed by the IDeA National Resource for Quantitative Proteomics, funded by the National Institute of General Medical Sciences (NIGMS) grant R24GM137786. This study was also supported by the Arkansas Children's Research Institute, the Arkansas Biosciences Institute, and the Center for Translational Pediatric Research funded under the National Institutes of Health National Institute of General Medical Sciences (NIH/NIGMS) grant P20GM121293 and the National Science Foundation Award No. OIA-1946391.”

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‘AJ - NIH grant 1P20GM135000-01A1 and the Louisiana State University, Department of Veterinary Clinical Sciences CORP grant

SB - Proteomic analysis was funded by the National Institute of General Medical Sciences (NIGMS) grant R24GM137786.

SB- Arkansas Children's Research Institute, the Arkansas Biosciences Institute, and the Center for Translational Pediatric Research funded under the National Institutes of Health National Institute of General Medical Sciences (NIH/NIGMS) grant P20GM121293 and the National Science Foundation Award No. OIA-1946391.”

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: Yes

Reviewer #2: 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 author compared the proteomes of 3 canine hepatobiliary neoplasms to normal hepatobiliary tissue, which is an attractive topic, as hepatobiliary neuroendocrine neoplasm is rare cancers in humans and primary hepatobiliary neoplasm omics studies is still lacking. The authors extracted proteins from canine hepatobiliary neoplasms and performed mass spectrometry analysis. The data showed that 32 proteins were up-regulated and 126 proteins were down-regulated. Among them, 6 up-regulated proteins were associated with non-hepatobiliary neuroendocrine tumors, 16 proteins were associated with neuroendocrine signal transduction, and 26 down-regulated proteins were enriched in altered metabolic pathways of cancer. However, I do not think at the current stage the article has a potential for consideration in the journal for the publication.

1. For screening up-regulated and down-regulated proteins in canine hepatobiliary neoplasms, in order to increase the persuasiveness of the article, it is recommended to add some experiments to verify the expression of significantly increased proteins.

2. I suggest, the clinical information should be added, such as patient classification.

3. Please add scale in Figure 2.

Reviewer #2: There is limited research on proteomics available in veterinary oncology. Furthermore, there are currently no studies evaluating proteomics in canine hepatobiliary neuroendocrine tumors. Thus, this manuscript begins to help fill the gaps in our understanding of these tumors. The introduction, materials and methods, results, and figures are complete and thorough.

I have one proposed revision for the discussion section. The limitations of utilizing FFPE samples as opposed to fresh frozen tissue samples should be addressed, as fresh frozen tissue is considered gold standard for comparative proteomics. Since FFPE samples are more common and overall reliable, I feel this information is still an important contribution to the current body of literature.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PONE-D-22-02231Reviewer comments.docx

Neoplastic signatures: comparative proteomics of canine hepatobiliary neuroendocrine tumors to normal niche tissue

PONE-D-22-02231R1

Dear Dr. Batts,

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,

Salvatore V Pizzo

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: I Don't Know

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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: (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: (No Response)

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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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