Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities

Round 1

Reviewer 1 Report

In this review study, Kulkarni et al translated the regulatory roles of ncRNAs in gastrointestinal cancer (GI) development, progression, chemoresistance, and health disparities. Moreover, these authors also emphasized the potential roles of ncRNAs as therapeutic targets and biomarkers, specifically concentrating on their ethnicity/race-specific prognostic value and discussing the prospects of genome-wide association studies (GWAS) to analyze the contribution of ncRNAs in GI tumorigenesis. I found this study interesting and relevant in the field.

Comments:

The topic is original and relevant in the field and addresses a specific gap in the field. I believe this review would be very useful for the clinical perspective on GI cancers.

I found that this study would provide new insight into the knowledge of GI tumorigenesis.

The article is well written.

The methodology is fine and no further control is required.

I found the conclusion to be in line with the evidence and arguments presented, and yes, the authors address the main question beautifully.

The tables are fine.

The references are well updated.

Minor points and suggestions:

Any review is hard to digest without the figures. Authors should provide at least a figure.

There is a study in preprint about gastric cancer (lncRNA GAS5/E2F1 and miR-34c), which is now under consideration in a journal (I found this study while reviewing this manuscript). We must give credit to the researchers when credit is due. Therefore,  the authors should have this study in their manuscript (10.21203/rs.3.rs-1599866/v2).

Author Response

In this review study, Kulkarni et al. translated the regulatory roles of ncRNAs in gastrointestinal cancer (GI) development, progression, chemoresistance, and health disparities. Moreover, these authors also emphasized the potential roles of ncRNAs as therapeutic targets and biomarkers, specifically concentrating on their ethnicity/race-specific prognostic value and discussing the prospects of genome-wide association studies (GWAS) to analyze the contribution of ncRNAs in GI tumorigenesis. I found this study interesting and relevant in the field.

Comments:

The topic is original and relevant in the field and addresses a specific gap in the field. I believe this review would be very useful for the clinical perspective on GI cancers. I found that this study would provide new insight into the knowledge of GI tumorigenesis. The article is well written. The methodology is fine and no further control is required. I found the conclusion to be in line with the evidence and arguments presented, and yes, the authors address the main question beautifully. The tables are fine. The references are well updated.

RE: Thank you for highlighting the key findings and the constructive comments.

Minor points and suggestions:

Any review is hard to digest without the figures. Authors should provide at least a figure.

RE: This was an important point and has been addressed by adding a figure illustrating ncRNA-mediated dysregulation of representative signal transduction pathways (Figure 1) to the revised version of the manuscript.

There is a study in preprint about gastric cancer (lncRNA GAS5/E2F1 and miR-34c), which is now under consideration in a journal (I found this study while reviewing this manuscript). We must give credit to the researchers when credit is due. Therefore, the authors should have this study in their manuscript (10.21203/rs.3.rs-1599866/v2).

RE: Thank you for your suggestion. We have cited 289 articles published within the last 10 years, and are not comfortable citing a pre-print that will need major revisions. The current version of the suggested pre-print is very difficult to read, Figure 2 is missing, and Figure 3 is incomplete in the file.

Reviewer 2 Report

The manuscript provides detailed and important insight to the involvement of non-coding RNAs in different GI cancers. It presents information on the signalling pathways that are regulated by ncRNAs together with comprehensive lists of known biomarker and therapeutic target candidate RNAs. Importantly, the race and ethnicity disparities in GI cancer patients are also mentioned, which is often neglected in similar reviews. 

The text is well-written and easy to follow, the tables are informative, although the organization principle behind the order of the RNAs is not clear, making it more difficult to get an overall picture.

I have only one suggestion: a table or figure summarizing the roles of ncRNAs in the different signal transduction pathways would help digesting the provided information and also connecting it to the other parts of the paper.

Author Response

Reviewer 2:

The manuscript provides detailed and important insight to the involvement of non-coding RNAs in different GI cancers. It presents information on the signalling pathways that are regulated by ncRNAs together with comprehensive lists of known biomarker and therapeutic target candidate RNAs. Importantly, the race and ethnicity disparities in GI cancer patients are also mentioned, which is often neglected in similar reviews. The text is well-written and easy to follow, the tables are informative, although the organization principle behind the order of the RNAs is not clear, making it more difficult to get an overall picture.

I have only one suggestion: a table or figure summarizing the roles of ncRNAs in the different signal transduction pathways would help digesting the provided information and also connecting it to the other parts of the paper.

RE: Thank you for your comments and suggestion. We have incorporated a figure to illustrate the roles of representative ncRNAs in different signal transduction pathways.