Review for 10.1186/s12876-020-01288-x (2020)

Reviewer ’s report  
 
Title: Identification of novel alternative splicing isoform biomarkers and their association with  
overall survival in colorectal cancer  
 
Version: 0 Date: 28 Aug 2019  
 
Reviewer: Patricia Coltri  
 
Reviewer's repo rt: 
 
Wang et al studied alternative splicing events in colorectal cancer. The problem analyzed is 
relevant and this paper might attract a broad audience, from researchers interested on data 
analysis, to those with a more clinical approach. The manuscript is gen erally well written, and 
deeply embraced by the data presented both in figures and supplementary material.  
The paper is scientifically sound; hypothesis, methods and analysis are clearly stated and 
controlled, which makes it an important contribution to th e field. However, I have some concerns 
that should be addressed. First, I noticed a lack of more recent papers on colorectal cancer and 
splicing. Also, concerning therapeutic targeting of spliceosome, there are papers that show 
mechanisms of splicing inhib ition that should be acknowledged (e.g. Pawellek, Bonnal, 
Effenberger, among others). The "Discussion" session is poor and do not refer to other papers, 
but is rather a summary of the main results. I suggest the Discussion to be re -written using 
literature  data to hold the major findings.  
"Results" session is generally well organized. About the CLK1 results, it is not clear to me 
whether this protein is essential or can be replaced by other CLKs. It is important to make this 
point clear because, as shown, the most common isoform in normal tissue is one that is directed 
to NMD. If this is true, then are there others that can modify SR proteins in normal tissues? Or 
are the authors suggesting these modifications occur only in cancer samples?  
The authors also  analyzed metastasis samples, finding specific splicing signatures. Concerning 
this analysis, is CD44 metastatic isoform non -functional? I missed some extra discussion on this 
point. Also concerning the metastasis sample analysis, the authors claim that FB NL2 exon 9 
skipping might be a specific event. However, one of the cancer samples (CRC2) shows the same 
phenotype. How "metastasis specific" is this event? Would it be possible that it is also found in 
other cancer samples?  
In my opinion Figure 1 is unnec essary. But if the authors decide to keep it, the caption needs to 
be better detailed.  
 
 
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please  specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript o r would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written Englis h 
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in  the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you receiv ed reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests i n relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests . 
 
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