Prognostic nutritional index as a prognostic factor for renal cell carcinoma: A systematic review and meta-analysis

Sung Ryul Shim; Sun Il Kim; Se Joong Kim; Dae Sung Cho

doi:10.1371/journal.pone.0271821

Peer Review History

Original SubmissionFebruary 10, 2022
29 May 2022 Decision Letter - Giuseppe Lucarelli, Editor PONE-D-22-03642Diagnostic Accuracy of Prognostic Nutritional Index as a Prognostic Factor for Renal Cell Carcinoma: A Systematic Review and Meta-AnalysisPLOS ONE Dear Dr. Cho, 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. Please submit your revised manuscript by Jul 13 2022 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. 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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide [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: Yes Reviewer #2: Partly Reviewer #3: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: 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: Yes Reviewer #2: No Reviewer #3: 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: Objectives: Authors aim for this systematic review and meta-analysis is to evaluate prognostic value of Prognostic Nutritional index by meta-analysis of the diagnostic test accuracy in kidney cancer. There are some minor issues that need to be corrected before the manuscript can be published. 1. The title of the introduction section should be modified (Itroduction) 2. The calculation formula of PNI is incorrect. I would ask the authors to correct it. 3. Figure 2 legend has a mistype error (“qualityof”) 4. In table 1 the authors wrote distal metastasis. Probably the authors meant distant. If it is the case, I would like to ask the authors to correct it. 5. In Figure 4 legend I believe that the acronym authors had intended to use is “SPEC” not “SEPC”. I would ask the authors to correct it. Reviewer #2: In the current manuscript the authors evaluated the diagnostic accuracy of the prognostic nutritional index (PNI) for renal cell carcinoma (RCC) in a pooled-analysis fashion. Overall the topic is interesting and timely, however, it is not new. Other groups reported SR & MA on PNI (DOI: 10.3389/fonc.2021.719941 - DOI: 10.1016/j.urolonc.2021.05.028) reaching the conclusion that PNI could be considered a potential prognostic predictor of treatment outcomes for patients with RCC. Neverthless, the authors of the current SR tried to slice the topic evaluating the diagnostic accuracy level only. Please find below some observation from my side. Abstract. Please remove the sentences "However, the prognostic value of PNI in RCC remains unclear.". It is absolutely not supported by the available literature. Abstract. Could authors clarify the period of paper collecting. Introduction. This sentence " Several prognostic factors for renal cell carcinoma (RCC) have been established, including the pathologic T stage, Fuhrman nuclear grade, tumor size, lymph node metastasis, and distant metastasis" needs strong references, indeed, the role of some of cited parameters are still under debate. Introduction. Could the author add a reference here "However, conflicting results have been reported regarding the utility of the PNI in patients with RCC, due to differences among studies in sample size, presence of metastasis, patient characteristics, and other factors." Introduction. A clear sentence about the aims of this study lacks. M&M. Please the authors provide the PICOS. Could the authors explain why they decided to include papers written in languages other than English. How were the articles traslated? M&M. The statistical analysis is reported in a remarkable way! Howeveer, the lack of RCT and High-level studies is a crucial negative-point. Results. Did the authors consider to evaluate ASA >2 patients as subgrup for the analysis? Please the authors report how to decide the variable for subgroup analysis. Discussion. Please absolutEly remove this sentences since they are not point of streight, but the normal way for addressing a SR-MA "The strengths of this study included the comprehensive literature search strategy based on a standardized protocol. Furthermore, rigorous data analysis methods were applied, such as bivariate random-effects meta-analysis (including covariates) and ROC curve analysis." Discussion. I believe that the discussion is the place where discuss about the results of analysis in a critical way. It is not the place where cut and paste the results of other work or talk about random arguments. Please handle it again. Conclusion. The conclusions are not supported by the results. They are not in line with the study aim that are to demonstrate the diagnostic accuracy of PNI as a prognostic factor for RCC References. They are up-to-date. However, several sentences in the manuscript lack references. Table and Figures. They are of good quality. Please a native speacker check is straight reccomanded. Reviewer #3: In this meta-analysis, the authors evaluated the role of the PNI as a prognostic factor for RCC. I have some comments: - Please rephrase the title and the text when you use the term "diagnostic" in association with "prognostic". For example in the title "diagnostic accuracy...as prognostic factor". Diagnosis and prognosis are different processes of medical evaluation. Please remove the term "diagnostic", in this study it has been evaluated the prognostic role of PNI. -A prognostic role has been proposed for other circulating biomarkers associated with different features of RCC biology, including carbonic anhydrase IX (CAIX), hypoxia-inducible factor-1α (HIF1α), CA15-3, PTX3, and C-reactive protein (CRP) (ref:PMID: 15126876; PMID: 24692843; PMID: 32345771;PMID: 20006861) These studies should be referenced and discussed. -RCC is a metabolic disease characterized by a reprogramming of energetic metabolism. In particular the metabolic flux through glycolysis is partitioned (PMID: 30983433, PMID: 29371925, PMID: 28933387; PMID: 30538212), and mitochondrial bioenergetics and OxPhox are impaired , as well as lipid metabolism (PMID: 30538212; PMID: 32861643). In addition a recent study (PMID: 33322148) delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. These findings should be referenced and discussed. ****** 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: Yes:** Tataru Octavian Sabin Reviewer #2: No Reviewer #3: 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.0271821.r001
Revision 1
6 Jul 2022 Author Response Thank you for your constructive comments and suggestions. We reviewed our manuscript and did all our best to revise the manuscript as you suggested. Those are as follows: Reviewer #1: 1) The title of the introduction section should be modified (Itroduction) Answer We thank the reviewer for this comment. We changed “Itroduction” to “Introduction” as reviewer suggested. 2) The calculation formula of PNI is incorrect. I would ask the authors to correct it. Answer We thank the reviewer for this important comment. We corrected the calculation formula of PNI as reviewer suggested. 3) Figure 2 legend has a mistype error (“qualityof”) Answer We thank the reviewer for this comment. We changed “qualityof” to “quality of” as reviewer indicated. 4) In table 1 the authors wrote distal metastasis. Probably the authors meant distant. If it is the case, I would like to ask the authors to correct it. Answer We thank the reviewer for this comment. We changed “distal” to “distant” as reviewer suggested. 5) In Figure 4 legend I believe that the acronym authors had intended to use is “SPEC” not “SEPC”. I would ask the authors to correct it.. Answer We thank the reviewer for this comment. We changed “SEPC” to “SPEC” as reviewer indicated. Reviewer #2: 1) Abstract. Please remove the sentences "However, the prognostic value of PNI in RCC remains unclear.". It is absolutely not supported by the available literature. Answer We thank the reviewer for this comment. We removed the sentences "However, the prognostic value of PNI in RCC remains unclear." In the abstract part of manuscript. 2) Abstract. Could authors clarify the period of paper collecting? Answer We thank the reviewer for this comment. To comply with the reviewer’s recommendations, we clarified the period of paper collecting in the abstract part of manuscript. 3) Introduction. This sentence " Several prognostic factors for renal cell carcinoma (RCC) have been established, including the pathologic T stage, Fuhrman nuclear grade, tumor size, lymph node metastasis, and distant metastasis" needs strong references, indeed, the role of some of cited parameters are still under debate. Answer We thank the reviewer for this important comment. To comply with the reviewer’s recommendation, we added references. In addition, we revised the sentence “have been established” to “have been established or under estimation”. 4) Introduction. Could the author add a reference here "However, conflicting results have been reported regarding the utility of the PNI in patients with RCC, due to differences among studies in sample size, presence of metastasis, patient characteristics, and other factors." Answer We thank the reviewer for this pertinent comment. To comply with the reviewer’s recommendations, we added references. In addition, we revised the term “conflict” to “insufficient”. 5) Introduction. A clear sentence about the aims of this study lacks. Answer We thank the reviewer for this important comment. To comply with the reviewer’s recommendations, we inserted the sentence “The aim of current study is to complete meta-analysis for diagnostic performance of PNI for the prediction of recurrence or survival in RCC patients, in order to provide more evidence-based data of PNI as a prognostic factor in RCC patients.” In the introduction part of manuscript. 6) M&M. Please the authors provide the PICOS. Answer We thank the reviewer for this pertinent comment. To comply with the reviewer’s recommendations, we inserted the sentence “Initial screening of search results based on titles and abstracts was performed based on structured questions using the PICO methodology: Populations: patients with RCC; Intervention: high PNI value; Comparator: low PNI value; Outcomes: survival” In the Methods part of manuscript. 7) Could the authors explain why they decided to include papers written in languages other than English. How were the articles traslated? Answer We thank the reviewer for this important comment. We tried to include all possible data because there were only a few papers about this topic. Therefore, we tried to include papers written in lanaguages other than English but unfortunately there was no suitable paper included in this study. 8) M&M. The statistical analysis is reported in a remarkable way! Howeveer, the lack of RCT and High-level studies is a crucial negative-point. Answer We thank the reviewer for this pertinent comment. We totally agree with the reviewer’s opinion. Therefore, we described it as a limitation point of this study in the discussion part of manuscript. 9) Results. Did the authors consider to evaluate ASA >2 patients as subgrup for the analysis? Please the authors report how to decide the variable for subgroup analysis.. Answer We thank the reviewer for this important comment. To comply with the reviewer’s recommendations, we performed subgroup analysis with ASA >2 patients. As a result of statistical analysis, there was no significant difference between ASA >2 group and ASA ≤2 group. In addtion, there were only 4 out of 11 studies showing ASA or ECOG score and limitation to the analysis. We described it in the result part of manuscript. We tried to perform subgroup analysis with variables for which data from all papers were available. As a result, these variables such as ethnicity, sample size, presence of metastasis, PNI cut-off value, QUADAS-2 classification, and proportion of males were included. 10) Discussion. Please absolutEly remove this sentences since they are not point of streight, but the normal way for addressing a SR-MA "The strengths of this study included the comprehensive literature search strategy based on a standardized protocol. Furthermore, rigorous data analysis methods were applied, such as bivariate random-effects meta-analysis (including covariates) and ROC curve analysis." Answer We thank the reviewer for this pertinent comment. To comply with the reviewer’s recommendations, we removed the sentences "The strengths of this study included the comprehensive literature search strategy based on a standardized protocol. Furthermore, rigorous data analysis methods were applied, such as bivariate random-effects meta-analysis (including covariates) and ROC curve analysis." In the discussion part of the manuscript. 11) Discussion. I believe that the discussion is the place where discuss about the results of analysis in a critical way. It is not the place where cut and paste the results of other work or talk about random arguments. Please handle it again. Answer We thank the reviewer for this important comment. To comply with the reviewer’s recommendation, we removed the sentence “We previously reported that a low PNI was strongly associated with tumor progression and poor prognosis in patients with non-metastatic RCC” and added the sentence “Therefore, the PNI can aid clinicians in predicting the clinical outcomes of RCC and patients with low PNI need to be managed by nutritional support and treated in a way to correct malnutritional status.” In the discussion part of the manuscript. 12) Conclusion. The conclusions are not supported by the results. They are not in line with the study aim that are to demonstrate the diagnostic accuracy of PNI as a prognostic factor for RCC Answer We thank the reviewer for this pertinent comment. To comply with the reviewer’s recommendations, we changed the sentence “In conclusion, the results of this study demonstrate that the PNI has value as a prognostic factor for RCC to “In conclusion, the results of this study demonstrate that diagnostic accuracy of the PNI as a prognostic factor for patients with RCC”. 13) References. They are up-to-date. However, several sentences in the manuscript lack references. Answer We thank the reviewer for this important comment. To comply with the reviewer’s recommendations, we added references in the sentences of the manuscript. 14) Table and Figures. They are of good quality. Answer We appreciate your trying to encourage us. 15) Please a native speacker check is straight reccomanded. Answer We thank the reviewer for this pertinent comment. However, our manuscript has already been qualified by an accredited institution. We attach the certificate file separately. Reviewer #3: 1) Please rephrase the title and the text when you use the term "diagnostic" in association with "prognostic". For example in the title "diagnostic accuracy...as prognostic factor". Diagnosis and prognosis are different processes of medical evaluation. Please remove the term "diagnostic", in this study it has been evaluated the prognostic role of PNI. Answer We thank the reviewer for this important comment. To comply with the reviewer’s recommendations, we removed the words “diagnostic accuracy of” from the title. However, this study is diagnostic test accuracy meta analysis and it is different from general meta analsysis in a method for statistical analysis. Therefore, we think it would be better to leave the word in an essential part of the text. 2) A prognostic role has been proposed for other circulating biomarkers associated with different features of RCC biology, including carbonic anhydrase IX (CAIX), hypoxia-inducible factor-1α (HIF1α), CA15-3, PTX3, and C-reactive protein (CRP) (ref:PMID: 15126876; PMID: 24692843; PMID: 32345771;PMID: 20006861) These studies should be referenced and discussed. Answer We thank the reviewer for this pertinent comment. To comply with the reviewer’s recommendations, we specifically discuss of circulating biomarkers associated with different features of RCC biology at the discussion section of the manuscript. 3) RCC is a metabolic disease characterized by a reprogramming of energetic metabolism. In particular the metabolic flux through glycolysis is partitioned (PMID: 30983433, PMID: 29371925, PMID: 28933387; PMID: 30538212), and mitochondrial bioenergetics and OxPhox are impaired , as well as lipid metabolism (PMID: 30538212; PMID: 32861643). In addition a recent study (PMID: 33322148) delineated a lipidomic profile of human ccRCC and integrated it with transcriptomic data to connect the variations in cancer lipid metabolism with gene expression changes. These findings should be referenced and discussed. Answer We thank the reviewer for this important comment. To comply with the reviewer’s recommendations, we more specifically discuss metabolism of RCC mentioned by reviewer in the discussion part of the manuscript. Attachments Attachment Submitted filename: Response to reviewers comments.docx https://doi.org/10.1371/journal.pone.0271821.r002
8 Jul 2022 Decision Letter - Giuseppe Lucarelli, Editor Prognostic Nutritional Index as a Prognostic Factor for Renal Cell Carcinoma: A Systematic Review and Meta-Analysis PONE-D-22-03642R1 Dear Dr. Cho, 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, Giuseppe Lucarelli, M.D., Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0271821.r003
Formally Accepted
27 Jul 2022 Acceptance Letter - Giuseppe Lucarelli, Editor PONE-D-22-03642R1 Prognostic Nutritional Index as a Prognostic Factor for Renal Cell Carcinoma: A Systematic Review and Meta-Analysis Dear Dr. Cho: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. 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 plosone@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. Giuseppe Lucarelli Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0271821.r004

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