A comprehensive analysis of ribonucleotide reductase subunit M2 for carcinogenesis in pan-cancer

Yong Wang; Rong Chen; Jing Zhang; Peng Zeng

doi:10.1371/journal.pone.0299949

Peer Review History

Original SubmissionOctober 21, 2023
18 Jan 2024 Decision Letter - Arthur J. Lustig, Editor PONE-D-23-34369A Comprehensive Analysis of Ribonucleotide Reductase Subunit M2 to Carcinogenesis in Pan-CancerPLOS ONE Dear Dr. Zeng, 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. The ability to peer-review a paper is dependent on the clarity of writing. In this regard, two issues must be dealt with before resubmission and re-review. In this regard, the manuscript requires a major improvement in English writing style and in clarity with respect to specific ideas as indicated by Reviewer 1. 2, While the issue of novelty pointed out by Reviewer 2 is not relevant for this journal, the authors should nonetheless identify which of the findings add to our current knowledge in the field. Please submit your revised manuscript by Mar 03 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. 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Thank you for stating the following financial disclosure: “This work was supported by the Jiangsu Provincial Special Program of Medical Science (BE2019750), National Natural Science Foundation of China (81827805), National Key Research and Development Program (2018YFA0704100, 2018YFA0704104), Science Fund for Creative Research Groups of the National Natural Science Foundation of China (61821002), and Interventional Radiology Scientific Research Special Fund Project of Jiangsu Medical Association (SYH-3201140-0025 (2021020)).” Please state what role the funders took in the study. If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. [Note: HTML markup is below. Please do not edit.] 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: Partly Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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 ****** 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: Yes ****** 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 study addressed the role of RRM2 in various tumors, which provide some interesting information for understanding carcinogenesis. There are some flaws needed to be addressed, as followings. 1- English should be carefully revised throughout the manuscript. 2- The quality of figures is very poor, and should be improved. 3- Introduction, page 3, line 22: “…to perform pan-cancer analysis of genes…” should be “…to perform a pan-cancer analysis of genes…” 4- Description of RRM2 gene expression should be in Italic and consistent through the manuscript. 5- Material and methods, page 4, line 78: “we chose…” should be “We chose…” 6- Material and methods, page 4, line 79: “…immune infiltrates of endothelial cell…” should be “…immune infiltrates of endothelial cells…” 7- Material and methods, page 5, line 97: “[24)” should be “[24]” 8- Material and methods, page 5, line 97: “pan-cencer” should be “pan-cancer” 9- Material and methods, page 4, “Genetic alteration analysis section”: In the analysis of RRM2 gene mutations, it is better to provide the accession number of RRM2 coding sequence used for the analysis. 10- Results, page 6, “RRM2 expression and clinical correlation in pan-cancer”: The authors examined the correlation between RRM2 expression and clinical characteristics of cancer patients, and found that RRM2 expression was significantly related to age, race, tumor stage, and status of cancer patients. It is better to describe in the main text, which age, race and tumor stage are associated with high RRM2 expression level. 11- Results, page 6, line 143-144: “…tumor patients’ clinical characteristics of patients with pan-cancer…” should be “…tumor clinical characteristics of patients with pan-cancer…” 12- Results, page 9, line 218: “…tumor mutational burden) TMB)…” should be “…tumor mutational burden (TMB)…” 13- Results, page 10, line 273: “…in Fig 7A We the…” should be “…in Fig 7A. We the…” 14- Discussion, page 13, lines 376-379: the authors found that “cell cycle”, “p53 signaling pathway”, “cell senescence, and other cellular pathways have potential roles in the effect of RRM2 on carcinogenesis. It is better to discuss these results according to the literature data. Reviewer #2: Numerous experimental studies have been conducted to show that RRM2 is associated with the occurrence and development of tumors. And the function and mechanism of RRM2 in tumors has also been relatively well studied. Therefore, this manuscript lacks novelty. ****** 6. 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 ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0299949.r001
Revision 1
29 Jan 2024 Author Response Response to Reviewers Reviewer #1: This study addressed the role of RRM2 in various tumors, which provide some interesting information for understanding carcinogenesis. There are some flaws needed to be addressed, as followings. 1-English should be carefully revised throughout the manuscript. A: I've done a native polish on the entire manuscript by Elsevier professional language polishing services. 2-The quality of figures is very poor, and should be improved. A: All the figures have been improved. 3-Introduction, page 3, line 22: “…to perform pan-cancer analysis of genes…” should be “…to perform a pan-cancer analysis of genes…” A: “…to perform pan-cancer analysis of genes…” has been modified into “…to perform pan-cancer analyses of genes…”according to Elsevier professional language polishing services. 4-Description of RRM2 gene expression should be in Italic and consistent through the manuscript. A: All description of RRM2 gene expression have be revised in Italic and consistent through the manuscript. 5-Material and methods, page 4, line 78: “we chose…” should be “We chose…” A: “we chose…” has been modified into “We chose…” 6-Material and methods, page 4, line 79: “…immune infiltrates of endothelial cell…” should be “…immune infiltrates of endothelial cells…” A: …immune infiltrates of endothelial cell…” has been modified into “…immune infiltrates of endothelial cells…” 7-Material and methods, page 5, line 97: “[24)” should be “[24]” A: “[24)” has been modified into “[24]” 8-Material and methods, page 5, line 97: “pan-cencer” should be “pan-cancer” A: “pan-cencer” has been modified into “pan-cancer” 9-Material and methods, page 4, “Genetic alteration analysis section”: In the analysis of RRM2 gene mutations, it is better to provide the accession number of RRM2 coding sequence used for the analysis. A: The number of RRM2 coding sequence is NC_000002.12NC_000002.12 10-Results, page 6, “RRM2 expression and clinical correlation in pan-cancer”: The authors examined the correlation between RRM2 expression and clinical characteristics of cancer patients, and found that RRM2 expression was significantly related to age, race, tumor stage, and status of cancer patients. It is better to describe in the main text, which age, race and tumor stage are associated with high RRM2 expression level. A: The clinical characteristics of patients have been described in the main text, which age, race and tumor stage are associated with high RRM2 expression level. 11-Results, page 6, line 143-144: “…tumor patients’ clinical characteristics of patients with pan-cancer…” should be “…tumor clinical characteristics of patients with pan-cancer…” A: “…tumor patients’ clinical characteristics of patients with pan-cancer…”have been modified into “…the clinical characteristics of patients with pan-cancer…”according to Elsevier professional language polishing services. 12-Results, page 9, line 218: “…tumor mutational burden) TMB) …” should be “…tumor mutational burden (TMB)…” A: “…tumor mutational burden) TMB)…” has been modified into “…tumor mutational burden(TMB)…” 13-Results, page 10, line 273: “…in Fig 7A We the…” should be “…in Fig 7A. We the…” A: “…in Fig 7A We the…” has been modified into “…in Fig 7A. We the…” 14-Discussion, page 13, lines 376-379: the authors found that “cell cycle”, “p53 signaling pathway”, “cell senescence, and other cellular pathways have potential roles in the effect of RRM2 on carcinogenesis. It is better to discuss these results according to the literature data. A: The “cell cycle”, “p53 signaling pathway”, “cell senescence, and other cellular pathways have potential roles in the effect of RRM2 on carcinogenesis. I discussed these results according to the literature data. Reviewer #2: Numerous experimental studies have been conducted to show that RRM2 is associated with the occurrence and development of tumors. And the function and mechanism of RRM2 in tumors have also been relatively well studied. Therefore, this manuscript lacks novelty. A: Indeed, many studies have reported the close relationship between RRM2 and tumorigenesis and development, but most of them still focus on tumor invasion and proliferation and corresponding signaling pathways and other tumor molecular mechanisms. In this paper, we have made a relatively new interpretation of the mechanism of RRM2 regulation of tumor from the perspective of the immune mechanism of RRM2 and tumor-infiltrating lymphocytes and immune checkpoint molecules, which may provide certain theoretical support for tumor immunotherapy. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0299949.r002
14 Feb 2024 Decision Letter - Arthur J. Lustig, Editor PONE-D-23-34369R1A Comprehensive Analysis of Ribonucleotide Reductase Subunit M2 for Carcinogenesis in Pan-CancerPLOS ONE Dear Dr. Zeng, 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 issue raised during the review process. Specifically, respond to Reviewer 2 with regard to a clarification on the rationale for the enrichment analysis of SND1-related partners. However you can ignore the comments about the resolution issues since the downloaded figures are sufficiently resolved. Please submit your revised manuscript by Mar 30 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Arthur J. Lustig, PhD Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] 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: (No Response) ******** 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: Yes ****** 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: Authors addressed the comments raised by this reviewer and this paper seems to be now ready for publication. Reviewer #2: 1. Why did "Enrichment analysis of SND1-related partners"? Is there a relationship of RRM2 and SND1? 2. Please consider to cite "" ext-link-type="uri" xlink:type="simple">https://doi.org/10.1016/j.gendis.2022.11.022". 3. All figures have to be uploaded in high resolution. ****** 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 ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0299949.r003
Revision 2
17 Feb 2024 Author Response Reviewer #2: 1. Why did "Enrichment analysis of SND1-related partners"? Is there a relationship of RRM2 and SND1? A: I'm very sorry. Thank you for your careful review. This is actually a clerical error on my part. It's actually “Enrichment analysis of RRM2-related gene”. I have already corrected all the relevant clerical errors in the Methods and Results. 2. Please consider to cite "https://doi.org/10.1016/j.gendis.2022.11.022". A: Sorry, I don't know what this link means and where to reference it. Besides, this link is typed to show AN ERROR with DOI NOT FOUND. 3. All figures have to be uploaded in high resolution. A: All figures have been uploaded in high resolution Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0299949.r004
21 Feb 2024 Decision Letter - Arthur J. Lustig, Editor A Comprehensive Analysis of Ribonucleotide Reductase Subunit M2 for Carcinogenesis in Pan-Cancer PONE-D-23-34369R2 Dear Dr. Zeng, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Arthur J. Lustig, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0299949.r005
Formally Accepted
21 Mar 2024 Acceptance Letter - Arthur J. Lustig, Editor PONE-D-23-34369R2 PLOS ONE Dear Dr. Zeng, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Arthur J. Lustig Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0299949.r006

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