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Thank you for revising your manuscript to address the concerns of the reviewers. The reviewers and I are satisfied with the revisions you have made in response to the various comments. The manuscript is now ready for publication.
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The authors addressed all my questions properly.
Please respond in detail to the comments from both reviewers
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The result presents an interesting investigation into the potential of GDF15 as a diagnostic biomarker for lung cancer. The results are presented in logical order. The study explores GDF15’s relationship with various factors like age, cancer subtypes, stages and established biomarkers. Here’s my review comments:
1- The paper is focused on GDF15 levels, authors should elaborate little more about mechanism of GDF15 action and why its level is elevated in lung cancer.
2- Author should focus about the advantage of GDF15 over the conventional biomarkers rather than superiority.
3- Author used only the ELISA test they should use al test one or two more analytic assay technique like W.B., fluorescence assay etc. to validate the ELISA result.
4- Why authors mentioned varied sample size for each biomarker. This is understandable but crucial to know. Did this variation arise randomly or because of some specific reason?
5- The authors used unit ng/ml for conventional biomarker but used pg/ml for GDF15 is there any special region for this if they use same unit for all biomarker.
6- Authors did not mention the age and other related supplementary data for the normal sample person in supplementary table regarding the age and GDF15.
7- Author should provide the same analysis figure-1A for the normal volunteer person.
8- Why the author used very few patient samples for 30-40 age group in supplementary table is there any specific region if not they should remove this data which make data more statistically significant.
9- Why the one week before and after time frame for biomarker data collection need to be explained. This can introduce variability.
10- Author did not mention anything about the effect of medication on the GDF15. Could this effect be of any medication?
11- I noticed that in supplementary table that most of the patient involve in this study was above 50 years age and very few are involved and there is no data below the 30 years. Author should explain about this?
12- Authors should include the citation (PMID: 31589613) in the reference list.
The study presents a valuable investigation into the diagnostic potential of GDF15 in lung cancer, filling a knowledge gap regarding its comparison with conventional biomarkers.
The manuscript was written in professional English, with sufficient background information provided. The manuscript presents well-labeled figures and tables that effectively support the data and conclusions.
However, the author should make sure all references follow consistent formatting. For example, ref 1 has a different format to others.
The study employs rigorous statistical analyses, including ROC curve analysis, to evaluate sensitivity and specificity, strengthening the credibility of the results. The inclusion of lung cancer subtypes (ADC, SCC, SCLC) and non-cancer groups (healthy individuals, benign tumors, pneumonia cases) improves the generalizability of the findings. The methods of this study were clearly stated, and the investigation meets a high technical & ethical standard.
However, the pneumonia group (n=2) is too small to yield meaningful comparative results. The study should either expand this group or acknowledge this limitation in the discussion.
The study includes patients who had already undergone treatment (e.g., chemotherapy, surgery), which may have influenced biomarker levels. This should be discussed as a limitation.
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