Comprehensive multi-omics analysis reveals prognostic, immune, and therapeutic signatures of TNFAIP family genes in breast cancer

Tahereh Barati; Madiheh Mazaheri Moghaddam; Fatemeh Mokhles; Zohreh Mirzaei; Amir Ebrahimi; Golsa Nayeb Ghanbar Hosseini; Najaf Allahyari Fard

doi:10.1371/journal.pone.0349012

Peer Review History

Original SubmissionOctober 21, 2025
16 Feb 2026 Decision Letter - Zeyneb Kurt, Editor -->PONE-D-25-56610-->-->Comprehensive multi-omics analysis reveals prognostic, immune, and therapeutic signatures of TNFAIP family genes in breast cancer-->-->PLOS One Dear Dr. Allahyari Fard, 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 Apr 02 2026 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 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, Zeyneb Kurt, PhD Academic Editor PLOS One Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. 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 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. Thank you for stating the following in the Competing Interests section: [During the preparation of this work, the authors used ChatGPT to improve readability and language skills. After using this tool, the authors carefully reviewed and edited the content as needed and took full responsibility for the content of the published article.]. Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: ""This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf. 3. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. [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: I Don't Know Reviewer #2: N/A ****** -->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: Yes Reviewer #2: No ****** -->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: The manuscript analyzes public available data in a comprehensive way to provide multiple potential correlation between TNFAIP and breast cancer. The results of analysis are informative. I only have a couple of suggestions. 1. It is not clear which subtypes of TNFAIP come from tumor cells, which types come from immune cells, and which types come from other cells. 2. The description and discussion of data seems not enough. For examples, Table 2 lists 10 top changed genes along with change of TNFAIP, none of them is mentioned in the manuscript. In addition, voltage-gated potassium channels are mentioned but there are no detailes of subtypes of these channels and potential roles. Reviewer #2: The authors of the manuscript presents a comprehensive in silico multi-omics analysis of the TNFAIP gene family in breast cancer (BC). They integrated transcriptomics, genomics, methylation, immune infiltration, and drug sensitivity using multiple public databases. The study is broad, systematic, and timely, and the topic is relevant. However, while the data mining is extensive, the manuscript currently overstates novelty and biological inference, lacks methodological rigor in multiple testing control, and would benefit from clearer mechanistic framing and validation logic. The substantial revisions, can help it become a good resource paper. 1. The statement that it's a first multiomics article in BC is too big to claim and needs to moderate it. 2. The stud lacks multiple testing control in crucial analysis. FDR correction is not consistent applied. This raises a chance of false positives. 3. The drug sensitivity analysis are mostly cell line based lacking patient data. 4. Although NF-κB, PI3K-Akt, and TNF signaling are highlighted, the manuscript does not provide causal models, integrated pathway analysis etc. 5. Several informations are repeated time and again in the manuscript which make it difficult to read and snthesisize a logical story. 6. Discussion need to be rewritten in more professional way. 7. A wet lab validation experiment will be really helpful. Overall, the manuscript need a major revision to be considered for publication. ****** -->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 ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. https://doi.org/10.1371/journal.pone.0349012.r001
Revision 1
12 Apr 2026 Author Response PONE-D-25-56610 Comprehensive multi-omics analysis reveals prognostic, immune, and therapeutic signatures of TNFAIP family genes in breast cancer Dear Editor and Reviewers, We sincerely thank you for your careful and thorough evaluation of our manuscript entitled “Comprehensive multi-omics analysis reveals prognostic, immune, and therapeutic signatures of TNFAIP family genes in breast cancer”, we greatly appreciate your detailed line-by-line feedback and constructive recommendations. Your comments have significantly improved the clarity, precision, and overall scientific presentation of our work. In response to reviewers, we have carefully revised the manuscript and addressed all concerns as detailed below. Response to Reviewer 1: 1. It is not clear which subtypes of TNFAIP come from tumor cells, which types come from immune cells, and which types come from other cells. We thank the reviewer for this important comment. The datasets used in this study are based on bulk transcriptomic data (TCGA and related resources), which include mixed signals from tumor, immune, and stromal cells. Therefore, our analysis does not allow precise determination of the cellular origin of TNFAIP expression. We have clarified this limitation in the Discussion section and noted that future single-cell or spatial transcriptomic studies will be required to define cell-type-specific expression patterns. 2. The description and discussion of data seems not enough. For examples, Table 2 lists 10 top changed genes along with change of TNFAIP, none of them is mentioned in the manuscript. In addition, voltage-gated potassium channels are mentioned but there are no detailes of subtypes of these channels and potential roles. We thank the reviewer for this constructive suggestion. We have now expanded the Discussion section to briefly describe the most relevant co-altered genes listed in Table 2 and their known roles in cancer biology. In addition, we have provided further clarification regarding the specific voltage-gated potassium channel subtypes identified in our enrichment analysis and discussed their potential functional relevance in breast cancer progression. These additions improve the biological interpretation of our findings. We once again sincerely thank you for your valuable time, insightful comments, and constructive feedback, which have greatly contributed to improving our manuscript, and we truly appreciate the opportunity to revise our work accordingly. Response to Reviewer 2: 1. The statement that it's a first multiomics article in BC is too big to claim and needs to moderate it. We thank the reviewer for this thoughtful comment. We agree that the original statement was too strong and have revised the manuscript to moderate this claim accordingly. 2. The stud lacks multiple testing control in crucial analysis. FDR correction is not consistent applied. This raises a chance of false positives. We thank the reviewer for highlighting the importance of multiple testing correction. In response, FDR adjustment using the Benjamini–Hochberg method has now been systematically applied to survival, methylation, and enrichment analyses where applicable. For analyses in which adjusted significance did not remain after FDR correction, the results have been revised accordingly and clearly indicated in the manuscript. In addition, a dedicated FDR column has been added to Supplementary Tables S1-S3 to ensure full transparency of adjusted significance values. 3. The drug sensitivity analysis are mostly cell line based lacking patient data. We thank the reviewer for this important observation. We acknowledge that the drug sensitivity analyses performed using GDSC and CTRP databases are primarily derived from cancer cell line data, which may not fully recapitulate the complexity of the tumor microenvironment in patient samples. This represents an inherent limitation of the currently available pharmacogenomic databases. We have added this limitation explicitly to the Discussion section. Validation of these findings using patient-derived organoids or clinical cohort data with treatment response information would be a valuable direction for future studies, and we highlight this as a priority for subsequent research. 4. Although NF-κB, PI3K-Akt, and TNF signaling are highlighted, the manuscript does not provide causal models, integrated pathway analysis etc. We thank the reviewer for this insightful comment. To address this concern, we have now added a new integrative conceptual schematic (Figure 8 replaced & previouse Figure 8, now is considered as Graphical Abstract) summarizing the multi-omics findings of our study, including expression, survival, immune infiltration, enrichment, and drug sensitivity analyses. This model provides a systems-level framework linking TNFAIP dysregulation to key signaling pathways in breast cancer. We have clarified in the Results section and in the figure legend that this model is conceptual and hypothesis-generating. Solid arrows represent associations identified in our analyses, while dashed arrows indicate mechanisms supported by prior experimental literature. No direct causal claims are made. 5. Several informations are repeated time and again in the manuscript which make it difficult to read and snthesisize a logical story. We thank the reviewer for this helpful comment. The manuscript has been carefully revised to reduce repetitive statements and improve overall coherence. Redundant descriptions of TNFAIP functions and pathway mechanisms were consolidated, and the Discussion section was reorganized to ensure a clearer and more logical progression of ideas. We believe these revisions have improved the readability and narrative flow of the manuscript. 6. Discussion need to be rewritten in more professional way. We appreciate the reviewer’s suggestion. The Discussion section has been thoroughly revised to improve clarity, scientific tone, and structural organization. We refined the language to ensure a more professional and concise presentation, reduced descriptive redundancy, and strengthened the interpretative focus of the section. We believe the revised Discussion now presents a clearer, more structured, and academically rigorous interpretation of our findings. 7. A wet lab validation experiment will be really helpful. We thank the reviewer for this valuable suggestion. We agree that experimental validation would further strengthen the biological relevance of our findings. The primary aim of this study was to provide a comprehensive multi-omics computational analysis of the TNFAIP family in breast cancer using publicly available datasets. Therefore, our results should be considered hypothesis-generating and serve as a foundation for future in vitro and in vivo investigations. Additionally, due to current resource and infrastructure limitations, experimental validation could not be performed within the timeframe of this study. We have now further clarified this point in the Discussion section. We sincerely thank the reviewer for the thoughtful and constructive feedback. The comments have greatly contributed to improving the quality and clarity of our manuscript, and we truly appreciate the opportunity to revise our work accordingly. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0349012.r002
15 Apr 2026 Decision Letter - Zeyneb Kurt, Editor -->PONE-D-25-56610R1-->-->Comprehensive multi-omics analysis reveals prognostic, immune, and therapeutic signatures of TNFAIP family genes in breast cancer-->-->PLOS One Dear Dr. Allahyari Fard, 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 May 30 2026 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 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. As the corresponding author, your ORCID iD is verified in the submission system and will appear in the published article. PLOS supports the use of ORCID, and we encourage all coauthors to register for an ORCID iD and use it as well. Please encourage your coauthors to verify their ORCID iD within the submission system before final acceptance, as unverified ORCID iDs will not appear in the published article. Only the individual author can complete the verification step; PLOS staff cannot verify ORCID iDs on behalf of authors. We look forward to receiving your revised manuscript. Kind regards, Zeyneb Kurt, PhD Academic Editor PLOS One Journal Requirements: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 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. Additional Editor Comments: The authors addressed all the comments & feedback from reviewers and/or the editor sensibly. However a link (http://bioinfo.life.hust.edu.cn/web/GSCALite/) to one of the tools used (GSCALite) is broken, which seems to have a working link on GitHub (https://github.com/chunjie-sam-liu/GSCALite). Can the authors please revise their manuscript and correct this issue with the broken link? [Note: HTML markup is below. Please do not edit.] [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 ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. --> https://doi.org/10.1371/journal.pone.0349012.r003
Revision 2
18 Apr 2026 Author Response Dear Editor and Reviewers, We sincerely thank you for your careful and thorough evaluation of our manuscript entitled “Comprehensive multi-omics analysis reveals prognostic, immune, and therapeutic signatures of TNFAIP family genes in breast cancer”, we greatly appreciate your detailed line-by-line feedback and constructive recommendations. Your comments have significantly improved the clarity, precision, and overall scientific presentation of our work. In response to journal requirements, we tried to meet every style criterion in the revised version additional to fixing declaration based on PLOS ONE policies. In response to reviewers, we have carefully revised the manuscript and addressed all concerns as detailed below. Response to Reviewer 1: 1. It is not clear which subtypes of TNFAIP come from tumor cells, which types come from immune cells, and which types come from other cells. We thank the reviewer for this important comment. The datasets used in this study are based on bulk transcriptomic data (TCGA and related resources), which include mixed signals from tumor, immune, and stromal cells. Therefore, our analysis does not allow precise determination of the cellular origin of TNFAIP expression. We have clarified this limitation in the Discussion section and noted that future single-cell or spatial transcriptomic studies will be required to define cell-type-specific expression patterns. 2. The description and discussion of data seems not enough. For examples, Table 2 lists 10 top changed genes along with change of TNFAIP, none of them is mentioned in the manuscript. In addition, voltage-gated potassium channels are mentioned but there are no detailes of subtypes of these channels and potential roles. We thank the reviewer for this constructive suggestion. We have now expanded the Discussion section to briefly describe the most relevant co-altered genes listed in Table 2 and their known roles in cancer biology. In addition, we have provided further clarification regarding the specific voltage-gated potassium channel subtypes identified in our enrichment analysis and discussed their potential functional relevance in breast cancer progression. These additions improve the biological interpretation of our findings. We once again sincerely thank you for your valuable time, insightful comments, and constructive feedback, which have greatly contributed to improving our manuscript, and we truly appreciate the opportunity to revise our work accordingly. Response to Reviewer 2: 1. The statement that it's a first multiomics article in BC is too big to claim and needs to moderate it. We thank the reviewer for this thoughtful comment. We agree that the original statement was too strong and have revised the manuscript to moderate this claim accordingly. 2. The stud lacks multiple testing control in crucial analysis. FDR correction is not consistent applied. This raises a chance of false positives. We thank the reviewer for highlighting the importance of multiple testing correction. In response, FDR adjustment using the Benjamini–Hochberg method has now been systematically applied to survival, methylation, and enrichment analyses where applicable. For analyses in which adjusted significance did not remain after FDR correction, the results have been revised accordingly and clearly indicated in the manuscript. In addition, a dedicated FDR column has been added to Supplementary Tables S1-S3 to ensure full transparency of adjusted significance values. 3. The drug sensitivity analysis are mostly cell line based lacking patient data. We thank the reviewer for this important observation. We acknowledge that the drug sensitivity analyses performed using GDSC and CTRP databases are primarily derived from cancer cell line data, which may not fully recapitulate the complexity of the tumor microenvironment in patient samples. This represents an inherent limitation of the currently available pharmacogenomic databases. We have added this limitation explicitly to the Discussion section. Validation of these findings using patient-derived organoids or clinical cohort data with treatment response information would be a valuable direction for future studies, and we highlight this as a priority for subsequent research. 4. Although NF-κB, PI3K-Akt, and TNF signaling are highlighted, the manuscript does not provide causal models, integrated pathway analysis etc. We thank the reviewer for this insightful comment. To address this concern, we have now added a new integrative conceptual schematic (Figure 8 replaced & previouse Figure 8, now is considered as Graphical Abstract) summarizing the multi-omics findings of our study, including expression, survival, immune infiltration, enrichment, and drug sensitivity analyses. This model provides a systems-level framework linking TNFAIP dysregulation to key signaling pathways in breast cancer. We have clarified in the Results section and in the figure legend that this model is conceptual and hypothesis-generating. Solid arrows represent associations identified in our analyses, while dashed arrows indicate mechanisms supported by prior experimental literature. No direct causal claims are made. 5. Several informations are repeated time and again in the manuscript which make it difficult to read and snthesisize a logical story. We thank the reviewer for this helpful comment. The manuscript has been carefully revised to reduce repetitive statements and improve overall coherence. Redundant descriptions of TNFAIP functions and pathway mechanisms were consolidated, and the Discussion section was reorganized to ensure a clearer and more logical progression of ideas. We believe these revisions have improved the readability and narrative flow of the manuscript. 6. Discussion need to be rewritten in more professional way. We appreciate the reviewer’s suggestion. The Discussion section has been thoroughly revised to improve clarity, scientific tone, and structural organization. We refined the language to ensure a more professional and concise presentation, reduced descriptive redundancy, and strengthened the interpretative focus of the section. We believe the revised Discussion now presents a clearer, more structured, and academically rigorous interpretation of our findings. 7. A wet lab validation experiment will be really helpful. We thank the reviewer for this valuable suggestion. We agree that experimental validation would further strengthen the biological relevance of our findings. The primary aim of this study was to provide a comprehensive multi-omics computational analysis of the TNFAIP family in breast cancer using publicly available datasets. Therefore, our results should be considered hypothesis-generating and serve as a foundation for future in vitro and in vivo investigations. Additionally, due to current resource and infrastructure limitations, experimental validation could not be performed within the timeframe of this study. We have now further clarified this point in the Discussion section. We sincerely thank the reviewer for the thoughtful and constructive feedback. The comments have greatly contributed to improving the quality and clarity of our manuscript, and we truly appreciate the opportunity to revise our work accordingly. Attachments Attachment Submitted filename: Response_to_Reviewers_auresp_2.docx https://doi.org/10.1371/journal.pone.0349012.r004
20 Apr 2026 Decision Letter - Zeyneb Kurt, Editor -->PONE-D-25-56610R2-->-->Comprehensive multi-omics analysis reveals prognostic, immune, and therapeutic signatures of TNFAIP family genes in breast cancer-->-->PLOS One Dear Dr. Allahyari Fard, 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 authors has not responded to the recent feedback given for their revised manuscript. The uploaded file and "responses to reviewers" seem to be repeating the responses given for the original version of the draft. Please see the comment given for their revised manuscript below and address this accordingly:--> The authors addressed all the comments & feedback from the reviewers sensibly. However, a link (http://bioinfo.life.hust.edu.cn/web/GSCALite/) to one of the tools used (GSCALite) is broken, which seems to have a working link on GitHub (https://github.com/chunjie-sam-liu/GSCALite). Can the authors please revise their manuscript and correct this issue with the broken link? =============================== Please submit your revised manuscript by Jun 04 2026 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 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. As the corresponding author, your ORCID iD is verified in the submission system and will appear in the published article. PLOS supports the use of ORCID, and we encourage all coauthors to register for an ORCID iD and use it as well. Please encourage your coauthors to verify their ORCID iD within the submission system before final acceptance, as unverified ORCID iDs will not appear in the published article. Only the individual author can complete the verification step; PLOS staff cannot verify ORCID iDs on behalf of authors. We look forward to receiving your revised manuscript. Kind regards, Zeyneb Kurt, PhD Academic Editor PLOS One Journal Requirements: 1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 2. 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. Additional Editor Comments : The authors has not responded to the recent feedback given for their revised manuscript. The uploaded file and "responses to reviewers" seem to be repeating the responses given for the original version of the draft. Please see the comment given for their revised manuscript below and address this accordingly: The authors addressed all the comments & feedback from the reviewers sensibly. However, a link (http://bioinfo.life.hust.edu.cn/web/GSCALite/) to one of the tools used (GSCALite) is broken, which seems to have a working link on GitHub (https://github.com/chunjie-sam-liu/GSCALite). Can the authors please revise their manuscript and correct this issue with the broken link? [Note: HTML markup is below. Please do not edit.] [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 ensure your figures meet our technical requirements, please review our figure guidelines: https://journals.plos.org/plosone/s/figures You may also use PLOS’s free figure tool, NAAS, to help you prepare publication quality figures: https://journals.plos.org/plosone/s/figures#loc-tools-for-figure-preparation. NAAS will assess whether your figures meet our technical requirements by comparing each figure against our figure specifications. --> https://doi.org/10.1371/journal.pone.0349012.r005
Revision 3
22 Apr 2026 Author Response Comment: The authors addressed all the comments & feedback from the reviewers sensibly.However, a link (http://bioinfo.life.hust.edu.cn/web/GSCALite/) to one of the tools used (GSCALite) is broken, which seems to have a working link on GitHub (https://github.com/chunjie-sam-liu/GSCALite). Can the authors please revise their manuscript and correct this issue with the broken link? Response: Thank you for pointing out the issue regarding the broken link in our manuscript. We have now corrected the broken link for GSCALite in our manuscript. As requested, we have replaced the previous URL with the active GitHub link (https://github.com/chunjie-sam-liu/GSCALite). Attachments Attachment Submitted filename: Response_to_Reviewers_auresp_3.docx https://doi.org/10.1371/journal.pone.0349012.r006
23 Apr 2026 Decision Letter - Zeyneb Kurt, Editor Comprehensive multi-omics analysis reveals prognostic, immune, and therapeutic signatures of TNFAIP family genes in breast cancer PONE-D-25-56610R3 Dear Dr. Allahyari Fard, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support. 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, Zeyneb Kurt, PhD Academic Editor PLOS One Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0349012.r007
Formally Accepted
Acceptance Letter - Zeyneb Kurt, Editor PONE-D-25-56610R3 PLOS One Dear Dr. Allahyari Fard, 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 You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. 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. Zeyneb Kurt Academic Editor PLOS One https://doi.org/10.1371/journal.pone.0349012.r008

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