PONE-D-21-19634

Bioinformatics analysis for the role of CALR in human cancers 

PLOS ONE

Dear Dr. Zhang,

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Academic Editor

PLOS ONE

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Additional Editor Comments (if provided):

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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: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: No

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: This manuscript by Li et al, comprehensively analyzed the role of CALR in cancers using GeneCards, UALCAN, GEPIA, Kaplan-Meier Plotter, COSMIC, Regulome Explorer, String,GeneMANIA and TIMER databases. The authors assess the possibility of CALR as a potential therapeutic target and survival biomarker. They studied the CALR expression in normal human tissues, various tumors and tumor stages. They found that mutations of CALR are widely present in tumors. CALR interacted with different genes and co-expressed with various proteins. In tumors, a variety of immune cells are closely related to CALR.

Here are my comments:

1. Please check for grammatical errors in the manuscript.

2. For the Kaplan-Meier Plotter, the link does not work.

3. In the results for figures 2,3,4 and 5, authors should conclude each section with why are there differences in CALR in different types of cancer?

4. The interpretation is not clear for figure 6. Please fix this.

5. Please cite the following articles:

a) Nitika, Blackman J.S., Knighton L.E., Takakuwa J.E., Calderwood S.K, Truman A.W. Chemogenomic screening identifies the Hsp70 co-chaperone DNAJA1 as a hub for anticancer drug resistance. Sci Rep 10, 13831 (2020).

b) itka Fucikova, Iva Truxova, Michal Hensler, Etienne Becht, Lenka Kasikova, Irena Moserova, Sarka Vosahlikova, Jana Klouckova, Sarah E. Church, Isabelle Cremer, Oliver Kepp, Guido Kroemer, Lorenzo Galluzzi, Cyril Salek, Radek Spisek; Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients. Blood 2016; 128 (26): 3113–3124.

Reviewer #2: This study utilizes multiple bioinformatics methods, however it lacks logical connections between analyses. Also the conclusion needs to be experimental validated. Comments are the following:

1.Line 146 Page 7, “the tissues with upregulated CALR mRNA in all three databases”. The “upregulated” is confusing, cause it is not clear what the author are comparing and what is set as control here.

2.Line 155 Page 8, The list of tumors seems redundant. It is more appropriate to show it in the table. In addition, the abbreviation for the tumor name is repeated in the figure legend (Figure 2 & 3).

3.Line 213 Page 10, it makes no sense to enumerate the percentage of each mutation in the different tumors and is lengthy. What is the conclusion for this part? And please use table for data presentation.

4.Line 213 Page 10, “CALR can be detected to be related to other genes”. The statement is ambiguous. What is the relationship and What are the other genes?

5.Line 252 Page 12, PPI and co-expressed proteins are two independent aspects of protein studies. It is unreasonable to summarize them together.

6.In Figure 8, what are the criteria for determining whether CALR expression is related to immune cell infiltration? Moreover, does the CALR gene expression here refer to the tumor cells or the immune cells?

7.The writing of this manuscript needs to be improved. Errors in grammar and typing need to be corrected. Besides, a colloquial expression should be avoided and statements is more accurate in written scientific language.

8.The resolution of the figures needs to be improved.

9.Overall, the data in this study was numerous, but did not reach a clear conclusion in the end. I would suggest that CALR gene should be studied in one specific tumor and validated experimentally.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: comment PONE-D-21-19634.docx

Bioinformatics analysis for the role of CALR in human cancers

PONE-D-21-19634R1

Dear Dr. Zhang,

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,

Bing He

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

Reviewer #2: 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

Reviewer #2: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: 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

Reviewer #2: Yes

**********

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

Reviewer #2: Yes

**********

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: The authors have addressed my comments and I recommend the manuscript for publication in this revised form.

Reviewer #2: (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

Reviewer #2: No