http://orcid.org/0000-0002-3082-1892
Peer Review History
| Original SubmissionNovember 18, 2019 |
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PONE-D-19-32000 Screening the p53 Connection of Cervical Cancer Pathogenesis Involving North-East Indian Patients. PLOS ONE Dear Dr. Husain, 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. ============================== ACADEMIC EDITOR: Brief methodologies needed for the conducted experiments and the image quality should be improvised. ============================== We would appreciate receiving your revised manuscript by 27th Feb 2020. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols Please include the following items when submitting your revised manuscript:
Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Kalimuthusamy Natarajaseenivasan Academic Editor PLOS ONE Journal Requirements: 1. When submitting your revision, we need you to address these additional requirements. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. 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9. Please clarify why ethical approval was not obtained from the ethical committee of Gauhati Medical College and Hospital, where patient samples were collected from 10. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type of consent you obtained (for instance, written or verbal). If your study included minors under age 18, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. [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 ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: No ********** 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: In the manuscript entitled “Screening the p53 Connection of Cervical Cancer Pathogenesis Involving North-East Indian Patients” the authors have discussed the mutation and expression aspects of p53 in cervical cancer pathogenesis Though the study is relevant as well as conceptually and methodologically sound, however suffers from writing and presentation issues, therefore need major revision. Some of the major and minor points are as follows: Abstract: Background: “Cervical cancer (CaCx) is a global issue” how?? Needs clarity Human papilloma virus should read: Human papillomavirus Blood was collected but how was it utilized is not mentioned?? Keywords: CaCx should be deleted Introduction: It is a leading cause of cancer related mortality in Indian women of both rural and urban areas?? Well breast cancer in India leads! Latest reference/ GLOBOCAN report should be referred First Para: last sentence “biomarker” to be deleted Ref. no. 8 and 9 do not relate to the statements made. The statement “The data in the role of dysregulated p53 in CaCx pathogenesis has been suggested, but differences exists in the data documented from different geographical niches” needs elaboration and citation. First page: last sentence: Tp53 should read: TP53 The statement “Genetic alterations in p53 gene have seldom been reported in carcinogenesis event [11]” is baffling. The authors should explain the ration behind this statement or it should be deleted. There is no dearth of reports on the genetic alterations of p53 in cancer. Last paragraph: Mizoram study??? Cancer of other etiology?? Which cancer?? Reference is missing?? The paragraph is ambiguous Materials and methods Enrolment of Patient and sample collection: Authors have discussed the processing of the samples. The title should be modified accordingly. Statement on ethical approval is missing. The ethnicity of the population needs clarity, and how the present population is different from the other population of their country. Did the patient samples (blood and biopsies) were collected by Gynaecologist or by the non-clinicians under the supervision of Gynaecologist. The statement needs to be reframed. Why blood was collected?? (for RNA bases study) ?? The following statement should be the part of results and not materials and methods “and based on the screening report, 84% (N=72) of cervical cancer cases were found to be HPV positive.” TP53 expression analysis Sybr green should be SYBR Green IHC: scoring system not mentioned TP53 Epigenetic profiling: the paired HPV positive cases (i.e. cases with both cancerous and noncancerous region) specifically for data specificity. Above statement is not clear: what about HPV negative cancer cases At many places Kit nomenclature is incomplete, country of origin is missing Several sites of TP53 known to be acetylated e. g, C-terminal K370, K372, K373, K381, K382, as well as K120, K164, K305 etc. However, rational of selection K305, K373 and K382 should be discussed. P53 Acetylation Study For which type Ab, WB and IHC was used?? Details should be provided here Results Demographical and clinical profile of the enrolled patients Clinical profile is missing. No association of the results with different stages of CaCx has been made and discussed Percentage missing in HPV results How stage III can be common to both low and high stages of cervical cancer: “lower severity stage (≤stage III) compared to higher stages of CaCx (≥stage III)” “To check the role of altered p53 gene in the susceptibility to CaCx the mutation study for six different exons (exon4�9) was done by PCR direct sequencing method (Fig 4A)” lacks clarity and should be reframed “The analysis result from the sequencing showed changes in exon4 of the p53 gene only in the affected region of the studied cases” ?? What is “the affected region of the studied cases” The following statement should be shifted to the discussion part. “This data suggests that p53 downreglation may probably a crucial early event in the pathogenesis of CaCx pathogenesis in HPV infected cases“ Following statement is the part of results and must be shortened and shifted to the discussion “Both the two isoforms of p53 due to polymorphism at codon 72 differ in biochemical and biological properties, especially in reference to its property of inducing apoptosis [19]. Sporadic report also is suggestive of the significance of HPV onco-protein E6 in targeted degradation of Arg72 p53, thereby altering cellular apoptosis and predisposing individuals to HPV-related cervical cancers [20]. Secondly, literature suggests that Arg/Pro germline heterozygotes is retained in squamous cell carcinomas and is more potent in neutralizing p73- induced apoptosis and also cooperates with other oncogenes to transform cells [21].” Both the two isoforms of p53?? “The data is therefore suggestive of the prognostic significance of the rs1042522 polymorphism in the studied population, and especially the Arg allele in HPV+ve cases” Must go to discussion When the cases where changes in p53 promoter methylation changes observed were considered ??? Needs clarity Acetylation also plays a key role in p53 protein stabilization and transcriptional regulations. Key acetylation sites which is associated with p53 transcript stability which inturn p53 protein expression K305, 373 and 382 was analyzed for differential expression with p53- acetylation specific antibodies by either western blot analysis (Ac-305) or by immunohistochemistry (Ac-372 and Ac-382). The above statement cannot be part of the results: half goes to MM and rest to discussion Discussion: Josefesson A et al. 1998 should read: Josefesson et al. (1998) There are many such incorrect citations throughout the manuscript “In Indian females belonging to both urban as well as rural area, cervical cancer has emerged to be major cause of cancer associated deaths” OR CaBr. Following statement is too long and lacks clarity “As per the National Centre for Disease Informatics and Research [24] based report on Cancer Burden in North Eastern States of India, the prevalence of cancer cervix in northeast India stands at 12.3 (10.1) [relative proportion %age (AAR)]; and more importantly, several districts of Arunachal Pradesh, Mizoram, Assam and Nagaland have high to very high distribution of the disease (rate per 100,000) and ranks amongst the highest prevalent areas or districts in India; making it a major health issue amongst females” “Although infection with high risk HPV strains has been underlined as the driving force in cervical cancer pathogenesis [25]. along with the data from the present studied cohort” What about high-risk HPV stains’ data in the present cohort. No mention has been made in the present study. Authors should provide data about high-risk HPVs analysed and their association. If northeast states are Arunachal Pradesh, Mizoram, Assam and Nagaland of India then from which state patients were recruited. Rational for selecting NE patients is not mentioed?? How this population ethinically differs from the other part of the country. Future comparative studies will other ethnic groups will be required to get a clear picture. This needs to be discussed. “Given the differences in cervical cancer distribution in different geographical subsets of populations with distinct and different ethnicity, the understanding of these key molecular and cellular factors becomes relevant and holds clinical significance” Reference is missing “Our findings correlate with several studies which demonstrates that in cervical cancer carcinogenesis the down-regulation of p53 levels is thought to be a key factor [26]” In the above statement authors says “several studies”, however only one reference has been cited and this reference is not a review article. What about p53 expression in HPV negative CaCx cases: No indication in results and discussion As cancer is known to be a multigene effect, how authors can signify the importance of only p53 and not the other genes. This needs to be argued. Table 1 . p53 should be italicised Table 2: Number of cases [%age]. % not calculated Table 2 and 3: CaCx should read: cervical cancer At many places figure legends are incomplete., e.g., Fig 4A What is Con?? Fig A, B,C?? The authors should avoid using “to check” frequencly. Instead, relevant synonyms should be used. There are innumerable full stops in-between the statements. e.g., Inactivation of p53 has been reported to be due to hyper-methylation of the promoter region [14]. and it has been associated with human neoplasia [15]. A review of English by a native English speaker or assistance from a professional English editing services is strongly recommended. Reviewer #2: Comments: The authors Khan et al. tried to explore the p53 connection of cervical cancer pathogenesis in North-east Indian patients by studying the complete p53 profiling including differential mRNA expression, immunohistochemistry, mutational status of p53 and also epigenetic profiling. In spite of a large number of publications on this subject, this manuscript carries importance as there is still a huge cervical cancer burden on the North-east Indian women which encourages the scientific community and researcher to continue the studies on cervical cancer. This manuscript has tried to find the significant role of p53 which is one of the most important tumor suppressor genes in CaCx patients of North-east Indian women. Going through the manuscript, I found several major concerns to be addressed by authors - 1. In the title the word ‘Screening’ may be replaced by words like ‘Evaluating’ or ‘Exploring’. 2. According to the statement made by the authors in the Introduction section that “The difference in the clinical presentation, the progression of the disease as well as response to treatment differs amongst individuals both with and without underlying HPV infection”, therefore both HPV positive and HPV negative CaCx cases carry equal significance for exploration of the mRNA expression for p53, however mRNA expression has only been studied for HPV positive CaCx cases by the authors. So what is the inference for HPV negative CaCx cases having downregulation of p53 mRNA expression? Comment. 3. In the Materials and Method section please mention what experiments were conducted with the blood samples collected from the patients. 4. Generally, 10% formalin is used for tissue fixation which contains 4% formaldehyde. So kindly comment on the utility of 4% formalin in tissue fixation. 5. Please provide brief protocol for each of the experiments conducted as per requirement of the journal. Also provide the details of the primary antibody against p53 used for IHC. 6. More rigorous statistical data needs to be furnished. 7. The distribution of the age group mentioned in the results section does not match with the table provided by the authors (Table 2). 8. The half life of the wild type p53 is very short and thus difficult to detect by IHC so the authors are requested to clarify whether the p53 detected by IHC for the study of differential p53 protein expression is wild type or mutated p53. 9. IHC images provided are low in resolution and lacking professional quality for publication. It is advised to include high resolution images containing arrows to mark the area of interest and scaling of the images. Moreover, please recheck the magnification mentioned in the images as it is written 400X and also the figure legends are not clear enough. Western blot images are not satisfactory. 10. The authors should comment on the limitation of the study as definite conclusion cannot be drawn from such small population of cases. ********** 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step.
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| Revision 1 |
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PONE-D-19-32000R1 Exploring the p53 Connection of Cervical Cancer Pathogenesis Involving North-East Indian Patients PLOS ONE Dear Dr. Husain, 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. We would appreciate receiving your revised manuscript by May 22 2020 11:59PM. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols Please include the following items when submitting your revised manuscript:
Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Kalimuthusamy Natarajaseenivasan Academic Editor PLOS ONE [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: All comments have been addressed ********** 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: No ********** 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: No ********** 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: In the manuscript entitled “Exploring the p53 Connection of Cervical Cancer Pathogenesis Involving North-East Indian Patients” the authors have discussed the mutation and expression aspects of p53 in cervical cancer pathogenesis The authors have satisfactory modified the manuscript. However, few minor concerns need to be addressed before final acceptance. Materials and methods: In: HPV screening and genotyping by PCR “using the specific primers for HPV16 1nd HPV” ???..Please clarify… “1nd” I am failing to understand that, when authors have performed HPV16 and 18 detection using type specific primers, then why the results pertaining to HPV16 and 18 frequencies have not been incorporated the results section. If at all cases were HPV16 positive than it should be highlighted in the results Moreover, the screening results of HIV, Hepatitis’s virus etc in the blood samples should be also highlighted. Further, the authors should clarify “etc” pathogens. A brief mention of methods of detection of “HIV, Hepatitis’s virus etc” should be made. Again the spelling of “Josefesson” is wrong in the text. It should read “Josefsson”. Authors should rigorously check the spelling of all the citations made in the text and reference list. Reviewer #2: Review Comments Response to query 2 I feel that the results which are not statistically significant should also be mentioned with p-values in the manuscript or else the information seems incomplete. Response to query 3 As mentioned by the author in the manuscript “Further the blood samples were used to screen the presence of any other pathogenic infection such as HIV, Hepatitis’s virus etc apart from HPV in the collected samples.” As per the above statement I would like to know whether HPV was tested from the blood samples. If so, please mention how one could assess the presence of HPV infection from blood samples. Response to query 6 Please include all the results with their statistical value in a single table format for better visualization and understanding. Response to query 8 As mentioned by the author the antibody used for immunohistochemistry was ab26 (abcam) however in the datasheet of the company it is mentioned that this antibody was not tested for IHC by the company. So, if you could kindly clarify and justify why this antibody was chosen for immunohistochemistry? Author has mentioned in the response 8 that “The antibody used i.e. ab26 (Abcam, UK) is anti-p53 monoclonal antibody capable of recognizing both mutant forms and wild-type human p53.” So I would like to know how you can differentiate which expression is due to mutant form and which is due to wild type human p53. ********** 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. |
| Revision 2 |
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Exploring the p53 Connection of Cervical Cancer Pathogenesis Involving North-East Indian Patients PONE-D-19-32000R2 Dear Dr. Husain, 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, Kalimuthusamy Natarajaseenivasan 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 Reviewer #3: All comments have been addressed Reviewer #4: All comments have been addressed ********** 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 Reviewer #3: Yes Reviewer #4: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: 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 Reviewer #3: Yes Reviewer #4: 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 Reviewer #3: Yes Reviewer #4: 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: (No Response) Reviewer #2: Response to query 8 is not satisfactory. As mentioned in the datasheet of the Antibody ab26 (abcam) under specificity that this antibody “recognizes an epitope that is structurally hidden in the wild type conformation of p53 but becomes exposed by denaturation or in mutant conformations of p53 where point mutations in the TP53 gene alter the structure of the protein”. Thus, I feel that the following author’s statement in result section “Similar to mRNA expression the expression of p53 protein was down-regulated in lower severity grade (≤ stage III) compare to higher severity grade (≥stage III) indicating its role in the initial stage of development of cervical cancer” is a bit controversial as this protein expression result by IHC with this antibody could also be interpreted as that the p53 mutation was more in higher severity grade and less in lower severity grade. So I think mRNA expression in this case cannot be supported by IHC with this antibody as stated in this paper rather it makes the result and discussion controversial. I would rather recommend omitting the IHC part or rewriting the result and discussion accordingly or redo the IHC part with more appropriate antibody. Reviewer #3: (No Response) Reviewer #4: The authors have addressed all the issues raised by other reviewer and the manuscript is suitable for publication. ********** 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 Reviewer #3: Yes: Dr Divya Uppala Reviewer #4: Yes: Amit Kumar Pandey |
| Formally Accepted |
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PONE-D-19-32000R2 Exploring the p53 Connection of Cervical Cancer Pathogenesis Involving North-East Indian Patients Dear Dr. Husain: 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. Kalimuthusamy Natarajaseenivasan Academic Editor PLOS ONE |
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