SUMO-Activating Enzyme Subunit 1 Is Associated with Poor Prognosis, Tumor Progression, and Radio-Resistance in Colorectal Cancer

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The researchers have done a good job.  But it seems like two separate studies joined into one. One part experimental and one part on patients.  I propose the following changes:

*The abstract does not explain what has been done in the article.  It should be rewritten to indicate the importance of SAE1 in the CRC.

Rewrite the methodology, results, discussion and conclusion as follows.  

*Methodology

**First the experiments performed on cells: cell type, media and culture conditions, and the experiments performed, in a clear and concise manner.

**Secondly, the experiments on mice.  Conditions and experiments performed. The following is explained in a clear and concise manner.

**Selection of patients and IHC.

*The same organisation can be followed in results, discussion and conclusion.  Thus, we can see the characterisation of SAE1 and its importance as a biomarker in CRC patients.

*The tables should be placed before the figures.  First we would see the information and then we would see the results graphically.

Comments on the Quality of English Language

 Minor editing of English language required

Author Response

The researchers have done a good job.  But it seems like two separate studies joined into one. One part experimental and one part on patients.  I propose the following changes:

*The abstract does not explain what has been done in the article.  It should be rewritten to indicate the importance of SAE1 in the CRC.

Rewrite the methodology, results, discussion and conclusion as follows.  

*Methodology

**First the experiments performed on cells: cell type, media and culture conditions, and the experiments performed, in a clear and concise manner.

**Secondly, the experiments on mice.  Conditions and experiments performed. The following is explained in a clear and concise manner.

**Selection of patients and IHC.

*The same organisation can be followed in results, discussion and conclusion.  Thus, we can see the characterisation of SAE1 and its importance as a biomarker in CRC patients.

*The tables should be placed before the figures.  First we would see the information and then we would see the results graphically.

 

 

Dear,

 

I hope this email finds you well. I would like to express my gratitude for the feedback provided on our manuscript titled "Characterization of SAE1 as a Biomarker in CRC Patients." Your insights are greatly appreciated, and we are committed to enhancing the clarity and coherence of our study.

 

We understand your suggestion of reorganizing the manuscript to better present our findings. After careful consideration, we have restructured the content in line with your recommendations. Below, we outline the revised approach for the methodology, results, discussion, and conclusion sections:

 

Methodology:

Our methodology has been revised for greater clarity, now comprising two distinct sections:

 

Experiments on Cells:

We have elaborated on the cell type, media, and culture conditions employed in our experiments. This section succinctly describes the specific experiments conducted on cells, ensuring a clear presentation of our methodology.

 

Experiments on Mice:

We now provide a concise overview of the conditions and experiments conducted on mice, following the cell-based experiments.

 

Patient Selection and Immunohistochemistry (IHC):

The selection criteria for patients and the detailed procedures for performing immunohistochemistry are now presented coherently in this subsection.

 

Table Placement:

Following your suggestion, we have reordered the tables to precede the figures, ensuring a more logical flow of information.

 

We believe that these revisions significantly enhance the organization and clarity of our manuscript. Your guidance has been invaluable, and we are confident that these changes will better highlight the importance of SAE1 as a biomarker in CRC patients.

 

Thank you once again for your thoughtful feedback. We are enthusiastic about the improvements made and are committed to delivering a manuscript that reflects the rigor and significance of our research.

 

Best regards,

 

Dr. Shang-Tao Chien

Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan

E-Mail: chienstkl@gmail.com

Tel.:+88674967515

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This is a large and potentially valuable study, however it is poorly described. The Abstract describes some general aspects of the treatment of colorectal cancer, but fails to focus on the study results. There are inconsistencies, for example  “In our study, SAE-1 was revealed to be an independent prognostic biomarker of CRC and was found to be associated with N-stage,” (the Abstract), while the Results say the opposite. It is unclear how % were calculated in Table 1. In Figure 3, si-SAE1 #1 and  si-SAE1 #2 are designated as si-SAE#1 and  si-SAE#2. The choice of the molecules in the Section 3.5 is not explained.    

The authors are strongly advised to find a colleague who has extensive experience in preparation of biomedical manuscripts and will agree to dedicate significant effort in the revision of this manuscript. The paper requires thorough re-writing in order to present the obtained data in a proper way.     

Comments on the Quality of English Language

Requires editing

Author Response

This is a large and potentially valuable study, however it is poorly described. The Abstract describes some general aspects of the treatment of colorectal cancer, but fails to focus on the study results. There are inconsistencies, for example  “In our study, SAE-1 was revealed to be an independent prognostic biomarker of CRC and was found to be associated with N-stage,” (the Abstract), while the Results say the opposite. It is unclear how % were calculated in Table 1. In Figure 3, si-SAE1 #1 and  si-SAE1 #2 are designated as si-SAE#1 and  si-SAE#2. The choice of the molecules in the Section 3.5 is not explained.    

The authors are strongly advised to find a colleague who has extensive experience in preparation of biomedical manuscripts and will agree to dedicate significant effort in the revision of this manuscript. The paper requires thorough re-writing in order to present the obtained data in a proper way.     

Dear,

 

Thank you for your insightful and constructive feedback on our manuscript titled " SAE1 regulated poor prognosis, tumor progression, and ra-dio-resistance in colorectal cancer." We greatly appreciate your thorough evaluation, which highlights areas that require clarification and refinement. We have carefully addressed your points to enhance the quality and coherence of our study.

 

Abstract Correction:

We acknowledge the inconsistency in the Abstract regarding the association of SAE-1 with N-stage. The statement "In our study, SAE-1 was revealed to be an independent prognostic biomarker of CRC and was found to be associated with N-stage" has been corrected to accurately reflect our findings.

 

Calculation of Percentages in Table 1:

Thank you for seeking clarification regarding the calculation of percentages in Table 1. We have ensured that the percentages presented in the table are calculated based on the total number of individuals, providing a clear understanding of the distribution.

 

Figure 3 Labeling Correction:

We apologize for the oversight in labeling si-SAE1 #1 and si-SAE1 #2 as si-SAE#1 and si-SAE#2 in Figure 3. The labeling has been rectified to accurately represent the experimental conditions.

 

Explanation for Choice of Molecules in Section 3.5:

We appreciate your observation regarding Section 3.5. The rationale for selecting specific molecules in this section has been added to provide a comprehensive understanding of our methodology.

 

We want to assure you that we take your feedback seriously, and your recommendations have significantly contributed to the improvement of our manuscript. We are dedicated to presenting our data in a clear and appropriate manner, ensuring that our study's significance shines through.

 

Thank you once again for your time and expertise in evaluating our work. We believe that these revisions will substantially enhance the manuscript's clarity and value.

 

Best regards,

 

Dr. Shang-Tao Chien

Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan

E-Mail: chienstkl@gmail.com

Tel.:+88674967515

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

The presented manuscript reveals that SAE-1 is an independent prognostic biomarker of CRC and was found to be associated with N-stage, M-stage, pathologic stage, recurrence, and overall survival time. In this publication, the authors declare that SAE1 knockdown inhibited CRC proliferation in vitro and in vivo, and led to the cleavage of PARP, downregulation of cyclin D1 protein expression, as well as downregulation of p-NF-κB/NF-κB. Additionally, SAE1 knockdown promoted radiosensitivity in CRC cells. Therefore, it was inferred that SAE1 may be used as a potential therapeutic target in CRC treatment.

Paper is written in a thoughtful and understandable way. It briefly summarizes the aim of the study and is divided into individual sections in which the authors accurately explain the carried out research. In terms of content, the information was presented fairly and accurately.

Moreover, there are not many works that describe the usefulness of SAE1 as a potential therapeutic target in CRC treatment in a similar way. Although the introduction of this parameter for everyday use in medicine requires a lot of additional research, as the authors point out in the Conclusions section, the presented manuscript is the valuable and interesting original article and I recommend this paper for publication.

Comments on the Quality of English Language

Minor editing of English language required.

Author Response

The presented manuscript reveals that SAE-1 is an independent prognostic biomarker of CRC and was found to be associated with N-stage, M-stage, pathologic stage, recurrence, and overall survival time. In this publication, the authors declare that SAE1 knockdown inhibited CRC proliferation in vitro and in vivo, and led to the cleavage of PARP, downregulation of cyclin D1 protein expression, as well as downregulation of p-NF-κB/NF-κB. Additionally, SAE1 knockdown promoted radiosensitivity in CRC cells. Therefore, it was inferred that SAE1 may be used as a potential therapeutic target in CRC treatment.

Paper is written in a thoughtful and understandable way. It briefly summarizes the aim of the study and is divided into individual sections in which the authors accurately explain the carried out research. In terms of content, the information was presented fairly and accurately.

Moreover, there are not many works that describe the usefulness of SAE1 as a potential therapeutic target in CRC treatment in a similar way. Although the introduction of this parameter for everyday use in medicine requires a lot of additional research, as the authors point out in the Conclusions section, the presented manuscript is the valuable and interesting original article and I recommend this paper for publication.

 

 

Dear,

 

I would like to express my sincere gratitude for your thoughtful and encouraging review of our manuscript titled " SAE1 regulated poor prognosis, tumor progression, and ra-dio-resistance in colorectal cancer." Your positive feedback is truly appreciated and motivating.

 

We are thrilled to hear that you found the manuscript's content to be both valuable and interesting. Your recognition of the significance of SAE-1 as an independent prognostic biomarker for CRC and its potential as a therapeutic target is incredibly rewarding. Your insightful observations regarding the correlations between SAE1 and key clinical parameters such as N-stage, M-stage, pathologic stage, recurrence, and overall survival time further validate the importance of our findings.

 

It is heartening to learn that our efforts in presenting the study in a clear and comprehensible manner have resonated with you. Your acknowledgment of the organization of the manuscript and our focused explanations of the conducted research are greatly appreciated.

 

Your recognition of the originality of our work, particularly in the context of exploring SAE1 as a potential therapeutic target in CRC treatment, reinforces our dedication to contributing valuable insights to the field. We wholeheartedly share your sentiment that while further research is necessary for the full integration of SAE1 in clinical practice, this study marks an important step towards that goal.

 

Your recommendation for the publication of our manuscript means a great deal to us. We are excited about the opportunity to share our findings with the broader scientific community and contribute to the ongoing advancements in CRC research.

 

Once again, thank you for your time, expertise, and thoughtful assessment of our manuscript. Your encouraging feedback inspires us to continue our efforts to expand our understanding of CRC and potential therapeutic avenues.

 

Best regards,

 

Dr. Shang-Tao Chien

Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan

E-Mail: chienstkl@gmail.com

Tel.:+88674967515

Reviewer 4 Report

Comments and Suggestions for Authors

Very interesting article, comprehensive presentation of methodology and results. 

The discussion could be improved.

A paragraph with study limitations should be added.

Author Response

Dear,

 

Thank you very much for your insightful feedback and your valuable time spent reviewing our article. We greatly appreciate your positive remarks on the comprehensive presentation of our methodology and results; your acknowledgment reinforces our commitment to delivering thorough and well-structured research.

 

We also appreciate your constructive criticism regarding the discussion section. Your input is invaluable to us, and we will certainly take steps to enhance the discussion by delving deeper into the implications of our findings and their relevance in the broader context of oral cancer research.

 

Furthermore, we would like to express our gratitude for emphasizing the importance of including a paragraph on study limitations. We have indeed taken your suggestion to heart and have incorporated a section in our manuscript discussing the limitations of our study. Specifically, we address the noteworthy issue of recurrence in oral cancer despite a higher overall survival rate and the absence of statistical results related to progression-free survival, which is pivotal for a comprehensive evaluation of treatment outcomes.

 

In addition, we acknowledge that while our study has illuminated the potential of SAE-1 in oral cancer treatment, the mechanistic exploration might have some limitations in terms of depth. Your encouragement to explore the underlying mechanisms in more detail aligns with our own aspirations for future research endeavors.

 

Once again, we deeply appreciate your time, expertise, and constructive feedback. Your valuable insights will undoubtedly contribute to the refinement and further development of our research. We are committed to addressing the discussed points and ensuring that the revised manuscript offers a more comprehensive and insightful contribution to the field of oral cancer research.

 

Best regards,

 

Dr. Shang-Tao Chien

Department of Pathology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan

E-Mail: chienstkl@gmail.com

Tel.:+88674967515

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

After the corrections, there is an improvement in the article with a better understanding of the article.  

Author Response

After the corrections, there is an improvement in the article with a better understanding of the article.  

We appreciate the improvements made, leading to a clearer understanding of the article. Thank you.

Reviewer 2 Report

Comments and Suggestions for Authors

Unfortunately, the authors did not take seriously my proposition to find someone, who is proficient in the preparation of biomedical manuscripts, and who will be willing to dedicate significant amount of time to the restructuring of this paper.

Even the Title contains a mistake “SAE1 regulated poor prognosis, tumor progression, and radio-2 resistance in colorectal cancer”. Did you want to say: “SAE1 is associated with …”.

The Abstract contains general information but largely fails to properly describe the results of the study. Again, there are multiple mistakes: “In vitro proliferation and radiosensitive assay were compared between control groups and SAE1 siRNA groups”. Do you mean “radiosensitivity assays”? Do you mean control and SAE1-inactive cells, not groups?

Comments on the Quality of English Language

Extensive editing of English language required

Author Response

Unfortunately, the authors did not take seriously my proposition to find someone, who is proficient in the preparation of biomedical manuscripts, and who will be willing to dedicate significant amount of time to the restructuring of this paper.

 

 

I understand your concern, and I want to clarify that we did seek assistance from two individuals who are well-versed in the preparation of biomedical manuscripts. Hung-Pei Tsai, an experienced researcher who has published numerous articles related to glioblastoma and similar topics, provided valuable insights. The structure of this article was influenced by his previous work, ensuring alignment with established standards in the field. Kuan-Ting Pan was specifically engaged to refine the manuscript's English language usage, improving its clarity and coherence. Despite these efforts, if there are still issues to address, the authors remain committed to further revisions to enhance the quality of the paper. Thank you for your feedback and understanding.

 

Even the Title contains a mistake “SAE1 regulated poor prognosis, tumor progression, and radio-2 resistance in colorectal cancer”. Did you want to say: “SAE1 is associated with …”.

 

Thank you for pointing that out. You are correct, and I apologize for the error. The correct title should indeed be "SAE1 is associated with poor prognosis, tumor progression, and radioresistance in colorectal cancer."

 

 

The Abstract contains general information but largely fails to properly describe the results of the study. Again, there are multiple mistakes: “In vitro proliferation and radiosensitive assay were compared between control groups and SAE1 siRNA groups”. Do you mean “radiosensitivity assays”? Do you mean control and SAE1-inactive cells, not groups?

 

Certainly, you're right. "SAE1 siRNA group" refers to cells in which SAE1 has been knocked down using siRNA. Thank you for the clarification, and I apologize for any confusion.

Round 3

Reviewer 2 Report

Comments and Suggestions for Authors

The authors did what they could do. The text is generally understandable and the scientific message is there. Extensive English scientific editing is still required to allow publication of this paper. Perhaps, some services may help in this respect.

Comments on the Quality of English Language

Extensive English scientific editing is still required to allow publication of this paper. Perhaps, some services may help in this respect.

Author Response

Thank you for your understanding and your recognition of the efforts we've put into improving the manuscript. We wholeheartedly agree that clear and concise language is essential for scientific communication.

In response to your suggestion, we have taken the necessary steps to ensure the manuscript meets the highest standards of language quality. We have utilized MDPI's English editing services to refine the text and address any language-related issues.

Attached to this message, you will find the proof of editing completion, which demonstrates our commitment to enhancing the paper's readability and overall quality. We believe that these revisions will significantly improve the manuscript's accessibility to the scientific community.
Your feedback and guidance have been instrumental in helping us enhance the manuscript, and we genuinely appreciate your support throughout this review process.

Once again, thank you for your valuable input and for recognizing our commitment to improving the manuscript's language and overall quality.

Best regards,

Author Response File: Author Response.pdf