Review Reports

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

It is a pleasure to review this insightful study. This paper systematically investigates the prognostic and predictive significance of Claudin‑6 expression in advanced‑stage high‑grade serous ovarian carcinoma, focusing on its association with platinum resistance and survival outcomes. The retrospective cohort design and standardized immunohistochemical evaluation provide clinically relevant insights into a promising therapeutic target. The study design is focused and the findings are meaningful for biomarker‑guided treatment. However, several methodological details and interpretive statements require minor revision to improve scientific rigor and reproducibility.

Minor revision:

• The authors should confirm the proportional hazards assumption for the Cox regression model with formal testing and report the results to validate the survival analysis.
• The current background lacks sufficient discussion of established clinical evidence; relevant literature must be added. The authors are suggested to cite two recently published studies (PMID: 39865831, PMID: 39289931) in the introduction section, as they are highly relevant to the background of this study.
• The claim that Claudin‑6 directly drives platinum resistance is slightly overstated; the authors should soften this causal interpretation in the conclusion.
• The authors should clarify the handling of missing data and the criteria for excluding patients to address potential selection bias in the retrospective cohort.
• The authors should refine the conclusion section to present the findings and contributions of the paper more clearly. Furthermore, please note the distinction between the conclusions and the abstract.
• Minor polishing of the English language and expression is recommended to further improve the clarity and readability of the manuscript. As presented, the writing is not acceptable for the journal. There are problems with sentence structure, verb tense, and clause construction.

Author Response

We sincerely thank the reviewer for the careful evaluation of our manuscript and for the constructive comments. We have revised the manuscript accordingly and addressed each point in detail below.

Comment 1.The authors should confirm the proportional hazards assumption for the Cox regression model with formal testing and report the results to validate the survival analysis.

Response 1.We thank the reviewer for this important methodological comment. The proportional hazards assumption was formally assessed using Schoenfeld residuals with the cox.zph function in R. The results indicated no significant violation of the proportional hazards assumption (global p = 0.053). This information has been added to the Methods and Results sections.

Comment 2.The current background lacks sufficient discussion of established clinical evidence; relevant literature must be added. The authors are suggested to cite two recently published studies (PMID: 39865831, PMID: 39289931) in the introduction section, as they are highly relevant to the background of this study.

Response 2.We thank the reviewer for this valuable suggestion. We have expanded the Introduction section to include a brief overview of previous studies investigating the role of CLDN6 in ovarian cancer. These additions provide better context for the clinical relevance of CLDN6 and strengthen the rationale of our study

Comment 3.The claim that Claudin‑6 directly drives platinum resistance is slightly overstated; the authors should soften this causal interpretation in the conclusion.

Response 3.We thank the reviewer for this insightful comment. We have revised the relevant statements in the manuscript to avoid causal interpretation and to better reflect an association rather than a direct effect. The wording has been carefully modified in both the Discussion and Conclusion sections.

Comment 4.The authors should clarify the handling of missing data and the criteria for excluding patients to address potential selection bias in the retrospective cohort.

Response 4.We thank the reviewer for this important comment. We have clarified the handling of missing data in the Methods section. Patients with missing key clinicopathological or survival data were excluded, and no imputation methods were applied. All analyses were conducted using complete-case data. This clarification has also been acknowledged in the Discussion section as a potential source of selection bias.

Comment 5.The authors should refine the conclusion section to present the findings and contributions of the paper more clearly. Furthermore, please note the distinction between the conclusions and the abstract.

Response 5.We thank the reviewer for this valuable suggestion. The Conclusion section has been revised to more clearly summarize the key findings and highlight the main contributions of the study.We have also ensured that the Conclusion is distinct from the Abstract by emphasizing interpretation, clinical relevance, and future implications rather than repeating detailed results.

Comment 6.Minor polishing of the English language and expression is recommended to further improve the clarity and readability of the manuscript. As presented, the writing is not acceptable for the journal. There are problems with sentence structure, verb tense, and clause construction.

Response 6.We thank the reviewer for this valuable comment. The manuscript has been carefully revised for English language, grammar, and clarity throughout. Sentence structure, verb tense, and overall readability have been improved to meet the journal’s standards.We believe that these revisions have significantly enhanced the clarity and quality of the manuscript.

Reviewer 2 Report

Comments and Suggestions for Authors

Congratulations to the authors on an interesting study of the prognostic and predictive significance of claudin-6 expression in advanced-stage high-grade serous ovarian carcinoma.

The article is well structured and organised.

My comments are as follows:

The introduction states that CLDN6 is “of considerable interest” but does not adequately summarise prior clinical studies in ovarian cancer. A brief review of previous CLDN6 studies in ovarian cancer should be added.

In the methods section, the inclusion and exclusion criteria are missing, and the exact follow-up duration is not specified. Otherwise, the study design appears appropriate.

The results are clearly presented.

The discussion is solid and balanced.

Author Response

We sincerely thank the reviewer for the positive and constructive evaluation of our manuscript. We appreciate the recognition of the study’s structure, clarity, and overall scientific contribution. All comments have been carefully addressed, and the manuscript has been revised accordingly.

Commets 1.The introduction states that CLDN6 is “of considerable interest” but does not adequately summarise prior clinical studies in ovarian cancer. A brief review of previous CLDN6 studies in ovarian cancer should be added.

Response 1.We thank the reviewer for this valuable suggestion. The Introduction section has been revised to include a brief overview of previous clinical studies investigating CLDN6 expression in ovarian cancer. These additions provide improved context for the biological and clinical relevance of CLDN6 and strengthen the rationale of our study.

Comments 2.In the methods section, the inclusion and exclusion criteria are missing, and the exact follow-up duration is not specified. Otherwise, the study design appears appropriate.

Response 2.We thank the reviewer for this important comment. The inclusion and exclusion criteria have now been clearly defined in the Methods section. In addition, detailed information regarding follow-up duration, including its definition and calculation using the reverse Kaplan–Meier method, has been added. These revisions improve the transparency and reproducibility of the study.

Comment 3.The results are clearly presented.

Response 3.We thank the reviewer for the positive evaluation of the Results section.

Comment 4.The discussion is solid and balanced.

Response 4.We appreciate the reviewer’s positive comments regarding the Discussion section.