Genomic Profiling and Molecular Characterization of Clear Cell Renal Cell Carcinoma
, Federica Ciciriello 1, Vittoria Musci 1, Francesco Salonne 1, Anna Ragno 2 and Mimma Rizzo 2,*
Round 1
Reviewer 1 Report
The authors should be congratulated for their work and for addressing an important topic. Only a few points warrant mention:
1. In the “Introduction” section, I suggest to include a statement on the adverse effects of VEGFR-TKIs and ICIs, such as in PMID: 37353178.
2. In the whole manuscript, especially in the “Introduction” and in the “Discussion and future perspective” the authors provide data on RCC and ccRCC, however, the real aim of the manuscript is to elucidate Genomic Profiling and Molecular Characterization of ccRCC, not on the other types. I suggest to report only data on ccRCC or to better explain the need to report data on the whole family of RCC.
3. In the “Discussion and future perspectives” section, by considering the potential role of liquid biopsy, the authors should include also microRNAs along with ccDNA. In this setting, I suggest this useful review: PMID: 37446024.
Author Response
The authors should be congratulated for their work and for addressing an important topic. Only a few points warrant mention:
> We would like to thank Reviewer#1 for his time reading our article, for his valuable suggestions and for his appreciation.
C1. In the “Introduction” section, I suggest to include a statement on the adverse effects of VEGFR-TKIs and ICIs, such as in PMID: 37353178.
A1. We have added the requested statement.
C2. In the whole manuscript, especially in the “Introduction” and in the “Discussion and future perspective” the authors provide data on RCC and ccRCC, however, the real aim of the manuscript is to elucidate Genomic Profiling and Molecular Characterization of ccRCC, not on the other types. I suggest to report only data on ccRCC or to better explain the need to report data on the whole family of RCC.
A2. We have clarified that almost all cited data refer to ccRCC. Many general RCC data have been better contextualised.
C3. In the “Discussion and future perspectives” section, by considering the potential role of liquid biopsy, the authors should include also microRNAs along with ccDNA. In this setting, I suggest this useful review: PMID: 37446024.
A3. We have added a statement on miRNA and their biomarker potential.
Reviewer 2 Report
In the current review, the authors summarize evidence for the genomic profiling and molecular characterization of clear cell renal cell carcinoma. They list prior studies on the molecular alterations of clinical interest in ccRCC, VHL and its network, mTOR and its network, chromatin remodeling modulators, DNA damage repair genes, cyclin-dependent kinases, and tumor mutation burden. The authors provided two interesting figures that summarize the tumor suppressive role of VHL, and the main chromatin remodeling systems involved in RCC tumorigenesis. Moreover, the authors provided one table that lists the principal clinical trials involving the HIF-2α inhibitor Belzutifan. From this discussion, the authors suggest that renal cell carcinoma does not have a single genomic predictive factor, but it is more likely to identify a signature of gene alterations that may influence its prognosis and treatment response.
Comments:
1) The provided sections read like narration for the evidence of discussed points without critical aspects/reflection points. At the end of each section, a take-home message is advised to be provided.
2) The authors should describe how they searched the literature, what are the keywords used, how many studies, and how did they select the proper studies (what are the inclusion/exclusion criteria for these studies?).
3) The authors are advised to make the figure caption stand-alone. To this end, authors are advised to provide the full names of all the listed abbreviations in the figures such as BAP1, SETD2, SWI/SN, etc. in Figure 2. Please, address this issue in all figures.
4) Careful revision of the reference list should be performed. For example, reference no. 29 lacks the unique identification number “2016 Aug 1;6(8):a026930”.
5) Likewise, reference no. 39 lacks the proper abbreviation of the journal name “JCO”. Instead, it should be written as “J Clin Oncol”.
Author Response
In the current review, the authors summarize evidence for the genomic profiling and molecular characterization of clear cell renal cell carcinoma. They list prior studies on the molecular alterations of clinical interest in ccRCC, VHL and its network, mTOR and its network, chromatin remodeling modulators, DNA damage repair genes, cyclin-dependent kinases, and tumor mutation burden. The authors provided two interesting figures that summarize the tumor suppressive role of VHL, and the main chromatin remodeling systems involved in RCC tumorigenesis. Moreover, the authors provided one table that lists the principal clinical trials involving the HIF-2α inhibitor Belzutifan. From this discussion, the authors suggest that renal cell carcinoma does not have a single genomic predictive factor, but it is more likely to identify a signature of gene alterations that may influence its prognosis and treatment response.
> We would like to thank Reviewer#2 for his time reading our article, for his valuable suggestions and for his appreciation.
C1. The provided sections read like narration for the evidence of discussed points without critical aspects/reflection points. At the end of each section, a take-home message is advised to be provided.
A1. We have added a take-home message at the end of each section.
C2. The authors should describe how they searched the literature, what are the keywords used, how many studies, and how did they select the proper studies (what are the inclusion/exclusion criteria for these studies?).
A2. In our narrative review, we searched for each gene (search term: 'gene name' in renal cell carcinoma) all articles available on the 'Pubmed' database and selected the most recent (from the last 10 years) and most cited studies (minimum number of citations: 10 citations) in which the clinical impact of the gene type was specifically assessed.
C3. The authors are advised to make the figure caption stand-alone. To this end, authors are advised to provide the full names of all the listed abbreviations in the figures such as BAP1, SETD2, SWI/SN, etc. in Figure 2. Please, address this issue in all figures.
A3. We have added abbreviations in captions.
C4. Careful revision of the reference list should be performed. For example, reference no. 29 lacks the unique identification number “2016 Aug 1;6(8):a026930”.
A4. References were revised.
C5. Likewise, reference no. 39 lacks the proper abbreviation of the journal name “JCO”. Instead, it should be written as “J Clin Oncol”.
A5. References were revised.
Reviewer 3 Report
The curroncol-2650842 is an interesting and appealing topic. The authors conducted a review investigating the mutational profile of clear cell RCC. The manuscript is of good quality.
The Introduction is complete and concise. All the necessary information regarding the backround of the molecular pathology behind ccRCC is included. The aim of the study is clearly mentioned.
The molecular alterations of clinical interest is well sub-categorized and properly analyzed. The quality of the figures and tables is helpful for the comprehension of the manuscript.
The discussion is of great quality and includes updated data. The milestones and limitations of treatment ccRCC are extensively analyzed, underlining the tumor heterogenity.
A conclusion section should be added.
Author Response
The curroncol-2650842 is an interesting and appealing topic. The authors conducted a review investigating the mutational profile of clear cell RCC. The manuscript is of good quality.
The Introduction is complete and concise. All the necessary information regarding the backround of the molecular pathology behind ccRCC is included. The aim of the study is clearly mentioned.
The molecular alterations of clinical interest is well sub-categorized and properly analyzed. The quality of the figures and tables is helpful for the comprehension of the manuscript.
The discussion is of great quality and includes updated data. The milestones and limitations of treatment ccRCC are extensively analyzed, underlining the tumor heterogenity.
> We would like to thank Reviewer #3 for taking the time to read our article, for his valuable suggestions and for his clear appreciation.
C1. A conclusion section should be added.
A1. We have added a 'Conclusions' section as suggested and consequently made some minor changes to the 'Discussion' section
Round 2
Reviewer 2 Report
The authors have adequately addressed the raised comments. Thanks!
