Reviewer ’s report  
 
Title: Secreted Protein Acidic and Rich in Cysteine -Like 1 Suppresses Metastasis in Gastric 
Stromal Tumors  
 
Version: 1 Date: 29 May 2018  
 
Reviewer: Paula Hurley  
 
Reviewer's report:  
 
In the manuscript BMGE -D18-00188R1, the authors show that decreased SPARCL1 expression 
in gastric GIST is associated with worse clinicopathological features.  The authors use in vitro 
and in vivo models to show that SPARCL1 has a r ole in restricting migration, invasion, and liver 
metastases. The manuscript would be improved by editing for grammar and by increased figure 
resolution.  
It is well established that decreased SPARCL1 expression is associated with worse 
clinicopathologic al features and outcomes in many adenocarcinomas including colorectal, 
gastric, and prostate. To the best of my knowledge, this is the first study to examine SPARCL1 
expression specifically in GISTs. The authors compare SPARCL1 expression by IHC in GISTs 
to normal gastric tissue. Unlike gastric adenocarcinoma, GISTs are thought to arise from cells of 
mesenchymal origin - interstitial cell of Cajal (ICC) or an ICC like precursor.  It is not clear that 
SPARCL1 expression is decreased in GISTs compared to ICCs , and it would strengthen this 
manuscript to show SPARCL1 expression in ICCs by IHC. The authors then show that 
SPARCL1 expression in GISTs is associated with PFS using univariate and multivariable cox 
proportional hazards modeling.  
The human -based data w ould be improved by more detailed descriptions.  There were a few 
discrepancies between the text and the tables.  For example, the text states that there was a 
significant correlation between SPARCL1 expression and NIH risk classification at the time of 
initial diagnosis, but Table 4 lists a non -significant P value.  In Table 5, the number of patients is 
not listed. The KM curves in Figure 4 would be improved by inclusion of at risk tables.   
The included lab -based experiments support the patient -based da ta.  These experiments validate 
what has been previously published in other cancer types, but do not add new mechanistic or 
biologic insights.   
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
  
Does the work include the necessary controls?  
If not,  please specify which controls are required in your comments to the authors.  
 
No 
 
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 manus cript or 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 English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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 stock s 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 received 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 in 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.  
 
I agree to the  open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses.  I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do  not wish to be included in my named report can be included as confidential comments 
to the  editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Secreted Protein Acidic and Rich in Cysteine -Like 1 Suppresses Metastasis in Gastric 
Stromal Tumors  
 
Version: 1 Date: 29 May 2018  
 
Reviewer: Paula Hurley  
 
Reviewer's report:  
 
In the manuscript BMGE -D18-00188R1, the authors show that decreased SPARCL1 expression 
in gastric GIST is associated with worse clinicopathological features.  The authors use in vitro 
and in vivo models to show that SPARCL1 has a r ole in restricting migration, invasion, and liver 
metastases. The manuscript would be improved by editing for grammar and by increased figure 
resolution.  
It is well established that decreased SPARCL1 expression is associated with worse 
clinicopathologic al features and outcomes in many adenocarcinomas including colorectal, 
gastric, and prostate. To the best of my knowledge, this is the first study to examine SPARCL1 
expression specifically in GISTs. The authors compare SPARCL1 expression by IHC in GISTs 
to normal gastric tissue. Unlike gastric adenocarcinoma, GISTs are thought to arise from cells of 
mesenchymal origin - interstitial cell of Cajal (ICC) or an ICC like precursor.  It is not clear that 
SPARCL1 expression is decreased in GISTs compared to ICCs , and it would strengthen this 
manuscript to show SPARCL1 expression in ICCs by IHC. The authors then show that 
SPARCL1 expression in GISTs is associated with PFS using univariate and multivariable cox 
proportional hazards modeling.  
The human -based data w ould be improved by more detailed descriptions.  There were a few 
discrepancies between the text and the tables.  For example, the text states that there was a 
significant correlation between SPARCL1 expression and NIH risk classification at the time of 
initial diagnosis, but Table 4 lists a non -significant P value.  In Table 5, the number of patients is 
not listed. The KM curves in Figure 4 would be improved by inclusion of at risk tables.   
The included lab -based experiments support the patient -based da ta.  These experiments validate 
what has been previously published in other cancer types, but do not add new mechanistic or 
biologic insights.   
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
  
Does the work include the necessary controls?  
If not,  please specify which controls are required in your comments to the authors.  
 
No 
 
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 manus cript or 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 English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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 stock s 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 received 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 in 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.  
 
I agree to the  open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses.  I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do  not wish to be included in my named report can be included as confidential comments 
to the  editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Secreted Protein Acidic and Rich in Cysteine -Like 1 Suppresses Metastasis in Gastric 
Stromal Tumors  
 
Version: 1 Date: 29 May 2018  
 
Reviewer: Paula Hurley  
 
Reviewer's report:  
 
In the manuscript BMGE -D18-00188R1, the authors show that decreased SPARCL1 expression 
in gastric GIST is associated with worse clinicopathological features.  The authors use in vitro 
and in vivo models to show that SPARCL1 has a r ole in restricting migration, invasion, and liver 
metastases. The manuscript would be improved by editing for grammar and by increased figure 
resolution.  
It is well established that decreased SPARCL1 expression is associated with worse 
clinicopathologic al features and outcomes in many adenocarcinomas including colorectal, 
gastric, and prostate. To the best of my knowledge, this is the first study to examine SPARCL1 
expression specifically in GISTs. The authors compare SPARCL1 expression by IHC in GISTs 
to normal gastric tissue. Unlike gastric adenocarcinoma, GISTs are thought to arise from cells of 
mesenchymal origin - interstitial cell of Cajal (ICC) or an ICC like precursor.  It is not clear that 
SPARCL1 expression is decreased in GISTs compared to ICCs , and it would strengthen this 
manuscript to show SPARCL1 expression in ICCs by IHC. The authors then show that 
SPARCL1 expression in GISTs is associated with PFS using univariate and multivariable cox 
proportional hazards modeling.  
The human -based data w ould be improved by more detailed descriptions.  There were a few 
discrepancies between the text and the tables.  For example, the text states that there was a 
significant correlation between SPARCL1 expression and NIH risk classification at the time of 
initial diagnosis, but Table 4 lists a non -significant P value.  In Table 5, the number of patients is 
not listed. The KM curves in Figure 4 would be improved by inclusion of at risk tables.   
The included lab -based experiments support the patient -based da ta.  These experiments validate 
what has been previously published in other cancer types, but do not add new mechanistic or 
biologic insights.   
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
  
Does the work include the necessary controls?  
If not,  please specify which controls are required in your comments to the authors.  
 
No 
 
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 manus cript or 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 English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections before being published  
 
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 stock s 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 received 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 in 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.  
 
I agree to the  open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses.  I agree for my report to be made available under an Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments 
which I do  not wish to be included in my named report can be included as confidential comments 
to the  editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant