PONE-D-24-19761Metastatic melanoma: An integrated analysis to identify critical regulators associated with prognosis, pathogenesis and targeted therapies

PLOS ONE

Dear Dr. Alizadeh,

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.

1. The manuscript does not seem to have conducted any non-computational experiments (or computational experiments to analyze the cohort from the author's institution). At the same time, GSE15605 is a relatively small data sample (12+16), which makes the generalizability of the results may not be proven. The author should consider explaining this part or adding necessary data/experiments to provide necessary evidence for generalizability.

2. Regarding the statement "The items recognized in the current study can be used as potential biomarkers for diagnostic, predictive, and might helpful to develop targeted combined therapies" mentioned in the manuscript. The experimental results do not seem to properly support the evidence mentioned in the manuscript. From my professional perspective, the manuscript seems to use virtual docking + molecular dynamics methods for analysis. As for molecular dynamics data, the relevant data of RMSF and SASA seem to be missing. As for the MMPBSA method, Figure 9 is very confusing, because such data may be more convincing in the form of a table. In addition, molecular dynamics does not seem to give a "conclusion". In addition, for example, Dabrafenib and MITF. In 2014, the FDA has approved Dabrafenib for use in patients with unresectable or metastatic melanoma with BRAF V600E mutations. To a certain extent, this coincides with the manuscript. In this context, is the addition of MITF a poly pharmacological effect? ​​Or is it just a "computational coincidence"? More importantly, will it provide a proven potential predictor for more precise targeted therapy? Compared with a mechanical view of the compound, these issues should be discussed or anticipated by the author.

3. I personally suggest that the manuscript should add a graphic Abstract to attract readers. And many of the manuscript's expression systems face major revisions (for example, some pictures are marked as Fig, and some are Figure).

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Ruo Wang

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PLOS ONE

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Additional Editor Comments:

The manuscript was highly praised by the peer reviewers. Congratulations : )

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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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: Yes

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5. Review Comments to the Author

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Reviewer #1: The manuscript entitled "

Metastatic melanoma: An integrated analysis to identify critical regulators associated

with prognosis, pathogenesis and targeted therapies" is interesting ,althought the manuscript lacks experimental data , but bioinformatic and statistical analysis are robust.

Reviewer #2: This is nice piece of research work. They have done a great job to identify genes or factors responsible for metastatic melanoma cancer. This is a dangerous disease for the human being. So, this research has a great impact on human health concerning skin disease.

Comment 1: Its ok. It will be great to confirm the function of the identified genes on metastatic melanoma cancer in biological manner as it is so important for disease treatment.

Reviewer #3: Paper titled Metastatic melanoma: An integrated analysis to identify critical regulators associated with prognosis, pathogenesis and targeted therapies are well documented and can beAccept in the present form

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Reviewer #1: Yes: Shahram Teimourian

Reviewer #2: Yes: Dr. Md Sohel Hasan, Professor, Dept. of Biochemistry and Molecular Biology, Rajshahi University, Bangladesh

Reviewer #3: Yes: Dr. Saumya Patel Gujarat University

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Metastatic melanoma: An integrated analysis to identify critical regulators associated with prognosis, pathogenesis and targeted therapies

PONE-D-24-19761R1

Dear Dr. Alizadeh,

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,

Ruo Wang

Academic Editor

PLOS ONE

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