PONE-D-22-04684Comprehensive analysis of Histone deacetylases genes in the prognosis and immune infiltration of glioma patientsPLOS ONE

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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: 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?

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

Reviewer #2: Yes

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4. 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

Reviewer #2: No

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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: In this study, the authors performed a Comprehensive analysis of Histone deacetylases genes in the prognosis and immune infiltration of glioma patients. Although the manuscript provides interesting findings, the way these are described need thorough editing. Below a number of points that have to be addressed before publication can be considered.

Introduction: Line no: 80 HWO should re-type as WHO.

Line no: 82 Reference 5 is not matching with the text.

Line no: 97 Reference 10 is not matching with the text. That paper talks about class I HDACs (HDAC1, HDAC2, HDAC3 and HDAC 8) not Class IIa HDACs (HDAC4, HDAC5 and HDAC7).

Figure legend Fig 1D and Fig 1E not matching with the figure. Figure legends 1F & 1G are missing.

In Fig 2A, the hazard ratio of HDAC2 and HDAC9 are almost similar. It’s not clear why they excluded HDAC2 from high risk group. (Moreover, HDAC1 and HDAC2 levels are significantly high in GBM when compared to normal brain- GEPIA data base).

Line no: 224- Typo error-The HDAC2, HDAC2 and HDAC10.

Line no:255; Should read as patients in TCGA and CGGA respectively.

Line no: 260; Should read as IDH mutation status, 1p19Q codeletion.

Line no: 269; Should read as IDH mutant and wild type.

Line no: 274 Should read as occurrence (primary or secondary).

Figure 5G-K not described in the results section.

Line no: 316: should read as year.

Line no:391: HDACs, as key enzymes that catalyze the acetylation of histones,???. Please correct the sentence.

Reviewer #2: This study by Shen et al. demonstrates that glioma patients can be divided into two subclasses

based on expression of eleven histone deacetylase (HDAC) genes, and patients from two subclasses had markedly different survival outcomes. Using multiple available data sets and bioinformatics approaches ((simple molecular subtyping and prognosis prediction-based methods), they established a prognostic model and identified six HDAC genes set (HDAC1, HDAC3, HDAC4, HDAC5, HDAC7, and HDAC9), as an independent prognostic factor in glioma patients. Furthermore, the calculated risk score which can predict well the five-year overall survival of glioma patients. It was also found that different survival outcomes of high- and low- risk patients could be linked with the differences of immune filtration level and tumor microenvironment. Finally, they also validated the prognostic model by measuring the expression levels of HDAC genes in RNA isolated form glioma patients’ tumors and non-tumor tissues samples.

This is a comprehensive analysis of glioma patients’ HDAC gene expression using TCGA and other sources data sets. This study provides new information that expression of a set of HDAC genes can be used to stratification of Glioma patients. Most of the conclusions are well supported by the results and presented data. However, there are few minor points which need further attention.

Minor comments:

Figure 9, the Pearson correlation analysis between different HDAC expression and patients’ resistance to different types of drugs is interesting. However, it is not clear while their data distributions patterns look very different, the correlation values for most of HDAC are very similar. For example, correlation of HDAC7 with Trametinib and HDAC4 with chelerythrine are very close p=0.47 and 0.45 but their distribution is very different. Please explain.

Figure 10, validation of the data by RT-PCR. Were these 23 samples of epilepsy patients used as normal brain tissues or there were from tumor adjacent tissues? It is not clear why the relative mRNA expression levels in Y axis have been presented in many arbitrary numbers such as 7, in some cases 8.5 for different HDAC. Some uniformity should be maintained in data presentation.

Page 12, line 121, HDAC2 was written two twice.

Legends of the corresponding figure has been embedded in the text of the results section. They need to be in a sperate section (Figure legend) in the text.

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Reviewer #1: No

Reviewer #2: No

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Comprehensive analyses reveal the role of histone deacetylase genes in prognosis and immune response in low-grade glioma

PONE-D-22-04684R1

Dear Dr. Li,

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.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Jinsong Zhang

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: Figure legends are fine now.

Manuscript typo errors have been rectified.

All comments have been addressed. Congratulations.

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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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