TP53 Mutation Mapping in Advanced Non-Small Cell Lung Cancer: A Real-World Retrospective Cohort Study
Round 1
Reviewer 1 Report
The study design is well constructed and the results are clearly presented.
It would be better to add a description of the considerations that explain the molecular biology of the results obtained in this study.
Author Response
Dear reviewer:
I am very grateful to your comments for the manuscript. According with your advice, I amend the relevant part in manuscript and hope meet with approval.
1. Moderate English changes required
Response: Thanks for the referee’s good evaluation and kind suggestion. I have carefully checked the entire manuscript for typographic, grammatical and formatting errors and hope that it is much more clear.
2. Are the results clearly presented?
Response: Thanks for the referee’s evaluation. I have checked the results part to ensure accuracy according to the comments.
3. Are the conclusions supported by the results?
Response: Thanks for the referee’s kind suggestion. Here, I have revised the conclusion to ensure its accuracy.
Comments and Suggestions for Authors:
The study design is well constructed and the results are clearly presented. It would be better to add a description of the considerations that explain the molecular biology of the results obtained in this study.
Response: Thanks for the referee’s good evaluation and kind suggestion. Existing evidence suggested that TP53 mutations may be vulnerable to immunotherapy approaches, an efficacy associated in particular with KRAS co-mutation, whereas the prognostic and predictive significance of EGFR/TP53 co-mutation in NSCLC patients remains controversial. Further study on the molecular biology is in progress.
Reviewer 2 Report
The authors have performed TP53 mutation mapping of 139 advanced NSCLC.
The results presented are very interesting and hypothesis generating.
Specific comments :
-78.4% of the tested tumors are TP53 mutated. This is quite high. Could the authors discuss this result ?
-Table 2 could be moved to the supplementary section
-Figure 4. DCB and NDB must be explained in the legend
-TP53 mutation was associated with TMB. Is smoking history the link between these factors ? The authors must perform a multivariate analysis.
Author Response
Dear reviewer,
I am very grateful to your comments for the manuscript. According with your advice, I amend the relevant part in manuscript and hope meet with approval.
1. Moderate English changes required
Response: Thanks for the referee’s suggestion. I have revised the relevant part and the manuscript has been reorganized according to the comments.
Comments and Suggestions for Authors:
1. 4% of the tested tumors are TP53 mutated. This is quite high. Could the authors discuss this result ?
Response: Thanks for the referee’s good evaluation. The discussion has been added in the related part.
2. Table 2 could be moved to the supplementary section.
Response: Thanks for the referee’s suggestion. In the study, we employed beneficial and noxious genes related with cancer treatment to evaluate their correlation with TP53wt and TP53mut and the manuscript has been reorganized according to the comments.
3. Figure 4. DCB and NDB must be explained in the legend.
Response: Here, the explanation of DCB and NDB had been added in the legend.
4. TP53 mutation was associated with TMB. Is smoking history the link between these factors ? The authors must perform a multivariate analysis.
Response: Thanks for the referee’s good evaluation and kind suggestion. Chronic mutagenic exposures (such as from tobacco) exhibit the highest prevalence of mutations. Accordingly, increased clinical outcomes suggest that TMB are driven by several factors, including DNA replication errors mediated by defective tumor suppressor genes (e.g.TP53), deficient DNA mismatch repair mechanisms, and including a history of smoking. Different from EGFR mutations, alteration in the TP53 gene, which functions as a tumor suppressor in response to mutagenic cellular stresses, is consistently associated with TMB level. However, the precise nature of this interaction, and the involvement of TMB, remain unclear. Recent work has been designed to elucidate the interaction between these factors to inform treatment decisions.
