A GNAS Gene Mutation’s Independent Expression in the Growth of Colorectal Cancer: A Systematic Review and Meta-Analysis

Round 1

Reviewer 1 Report

The authors used a systematic review and meta-analysis of multiple studies methods to link the poor prognosis of CRC and the GNAS mutations. Overall, the manuscript is well written. I suggest accepting after minor reversion.

1: GNAS's full name when first mentioned in the abstract and manuscript.

2: Some letters in Figure 1 and Table 1 are missing, please double-check and make sure all letters are visible. 

 

Author Response

Thank you, dear reviewer. Your comments and suggestions were well addressed and the revised edition will be uploaded and re-submitted. Thank you

GNAS's full name when first mentioned in the abstract and manuscript.	Thank you, dear reviewer, for your comments. The full name of GNAS has been written in the abstract as suggested.
Some letters in Figure 1 and Table 1 are missing, please double-check and make sure all letters are visible.	Thank you, dear reviewer, for your comments. The authors have restructured the concerned tables and figures as requested by the reviewers. Missing data has been rewritten and the table made more readable.

Author Response File: Author Response.docx

Reviewer 2 Report

This study performed a metaanalysis of the presence of mutations in GNAS around the world. It shows that the prevalence differs according to the geographical regions. These results are useful to consider if the mutations could be related to outcomes and useful as markers.  The meta-analysis was well performed and the manuscript was well-written.

 

Only minor revision;

1. Table 1 is unreadable.

2. Because mutation of GNAS can be in It could be also interesting to see which mutations are predominant (other than R201C or R201H)

3. Please discuss briefly in introduction about mutation on locus R201C or R201H

4. I would like to confirm why the authors exclude "research that examined just one of either codon R201C or R201H of GNAS gene mutation"  if finally the analysis for each mutation is performed separately.

Author Response

Thank you, dear reviewer. Your comments and suggestions were well addressed and the revised edition will be uploaded and re-submitted. Thank you

Reviewers’ comments	Author s reply
Table 1 is unreadable	Thank you, dear reviewer, for your comments. Table 1 has been re-structured to make it clearer and more readable
Because mutation of GNAS can be in It could be also interesting to see which mutations are predominant (other than R201C or R201H)	Thank you, dear reviewer, for your comments. Your suggestion is well noted and appreciated dear reviewer and the author totally agreed with your suggestion. However, in this particular study, the R201C and R201H are the most exclusively most commonly reported mutation in the GNAS gene, together, both are responsible for about 60-80% of all sub-GNAS mutations but, as for which of the two is most predominant, both occurrences are almost in similar proportion, but they exclusively occur in GNAS mutation
Please discuss briefly in the introduction about mutation on locus R201C or R201H	Thank you, dear reviewer, for your comments. A discussion on R201C and R201H has been incorporated into the introduction paragraph as suggested by the reviewer
I would like to confirm why the authors exclude "research that examined just one of either codon R201C or R201H of GNAS gene mutation"  if finally the analysis for each mutation is performed separately	Thank you, dear reviewer, for your comment. It was actually an oversight, we initially planned to investigate GNAS mutation occurrence from studies that did not restrict mutation assessment to a particular sub codon. The statement has been deleted as all studies that report on GNAS mutation regardless of the sub codon were included in our study.

Author Response File: Author Response.docx

Reviewer 3 Report

The authors explored the expression of GNAS gene mutation in colorectal cancer by means of a systematic review and meta-analysis.

The manuscript is well-written and the study seems scientifically sound. The paper can be accepted following minor revisions to the content.

Some suggestions for revision are listed below:

- a minor polishing of the English language is required 

- if you define an abbreviation, please be consistent and use it throughout the study, e.g., CRC

- pubmed is not a database, it is a search service. The database is MEDLINE

- some of the methods and results related to the methodology evaluation can be presented as a supplementary file if not really relevant to the findings

- please revise the table and figure to show up correctly, the text is truncated 

- the references are not correctly formatted and ciyed within the text. Please check MDPI guidelines - American chemical society format is needed

- please.add a paragraph in the discussion in which you discuss the clinical relevance of your findings and how we can integrate it in patient management

 

Author Response

Thank you, dear reviewer. Your comments and suggestions were well addressed and the revised edition will uploaded and re-submitted. Thank you

Author Response File: Author Response.docx