Title: Identification and validation of a lenvatinib resistance-related prognostic signature in
HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Version: 3 Date: 02 Mar 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: Identification and validation of a lenvatinib resistant-related prognostic signature in HCC,
in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Thank you for the opportunity to review your manuscript. The study presents a well-structured
and detailed investigation into lenvatinib resistance in hepatocellular carcinoma (HCC), offering
valuable insights into predictive gene signatures. Your integration of bioinformatics analysis
with in vitro validation significantly enhances the study’s credibility and potential impact.
The introduction provides a clear rationale for the study, emphasizing the clinical challenge
of lenvatinib resistance and the necessity for predictive biomarkers. The background section
is comprehensive, summarizing current knowledge while highlighting gaps in research that
your study aims to address. The justification for focusing on lenvatinib resistance-related
differentially expressed genes (LRRDEGs) is well-explained, and the use of multiple publicly
available datasets strengthens the study’s foundation.
the discussion could benefit from additional clarity regarding the limitations of using in
silico analyses for risk score development and how patient heterogeneity may impact model
performance in diverse clinical settings.
The clinical applicability of the LRRPS model could be discussed further. While the nomogram
offers predictive utility, it would be helpful to include a discussion on its potential integration
into clinical decision-making and whether prospective validation in patient cohorts is planned.
Additionally, while the in vitro experiments provide strong evidence for PFKFB4’s role in
lenvatinib resistance, further mechanistic studies, such as rescue experiments, would enhance the
causal inference. Finally, the manuscript contains some typographical and grammatical errors
that should be corrected for clarity and readability.
Additionally consider adding the supplementary figures into the main manuscript.
Best regards.
Title: Identification and validation of a lenvatinib resistance-related prognostic signature in
HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Version: 3 Date: 02 Mar 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: Identification and validation of a lenvatinib resistant-related prognostic signature in HCC,
in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Thank you for the opportunity to review your manuscript. The study presents a well-structured
and detailed investigation into lenvatinib resistance in hepatocellular carcinoma (HCC), offering
valuable insights into predictive gene signatures. Your integration of bioinformatics analysis
with in vitro validation significantly enhances the study’s credibility and potential impact.
The introduction provides a clear rationale for the study, emphasizing the clinical challenge
of lenvatinib resistance and the necessity for predictive biomarkers. The background section
is comprehensive, summarizing current knowledge while highlighting gaps in research that
your study aims to address. The justification for focusing on lenvatinib resistance-related
differentially expressed genes (LRRDEGs) is well-explained, and the use of multiple publicly
available datasets strengthens the study’s foundation.
the discussion could benefit from additional clarity regarding the limitations of using in
silico analyses for risk score development and how patient heterogeneity may impact model
performance in diverse clinical settings.
The clinical applicability of the LRRPS model could be discussed further. While the nomogram
offers predictive utility, it would be helpful to include a discussion on its potential integration
into clinical decision-making and whether prospective validation in patient cohorts is planned.
Additionally, while the in vitro experiments provide strong evidence for PFKFB4’s role in
lenvatinib resistance, further mechanistic studies, such as rescue experiments, would enhance the
causal inference. Finally, the manuscript contains some typographical and grammatical errors
that should be corrected for clarity and readability.
Additionally consider adding the supplementary figures into the main manuscript.
Best regards.
Please review this paper.
user
Title: Identification and validation of a lenvatinib resistance-related prognostic signature in
HCC, in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Version: 3 Date: 02 Mar 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: Identification and validation of a lenvatinib resistant-related prognostic signature in HCC,
in which PFKFB4 contributes to tumor progression and lenvatinib resistance
Thank you for the opportunity to review your manuscript. The study presents a well-structured
and detailed investigation into lenvatinib resistance in hepatocellular carcinoma (HCC), offering
valuable insights into predictive gene signatures. Your integration of bioinformatics analysis
with in vitro validation significantly enhances the study’s credibility and potential impact.
The introduction provides a clear rationale for the study, emphasizing the clinical challenge
of lenvatinib resistance and the necessity for predictive biomarkers. The background section
is comprehensive, summarizing current knowledge while highlighting gaps in research that
your study aims to address. The justification for focusing on lenvatinib resistance-related
differentially expressed genes (LRRDEGs) is well-explained, and the use of multiple publicly
available datasets strengthens the study’s foundation.
the discussion could benefit from additional clarity regarding the limitations of using in
silico analyses for risk score development and how patient heterogeneity may impact model
performance in diverse clinical settings.
The clinical applicability of the LRRPS model could be discussed further. While the nomogram
offers predictive utility, it would be helpful to include a discussion on its potential integration
into clinical decision-making and whether prospective validation in patient cohorts is planned.
Additionally, while the in vitro experiments provide strong evidence for PFKFB4’s role in
lenvatinib resistance, further mechanistic studies, such as rescue experiments, would enhance the
causal inference. Finally, the manuscript contains some typographical and grammatical errors
that should be corrected for clarity and readability.
Additionally consider adding the supplementary figures into the main manuscript.
Best regards.
assistant