Title: Downregulation of SMOC1 is associated with progression of colorectal traditional
serrated adenomas
Version: 1 Date: 22 Dec 2023
Reviewer's report:
The findings from this comprehensive study confirm the authors earlier work published in 2018
showing that SMOC1 is silenced by methylation in TSAs and also in conventional adenomas
and SSLs when they develop high grade dysplasia.  The methods are sound and the data clearly
presented.  There are some specific comments:
1.  The term high grade adenoma is confusing - the usual convention for adenomas with these
characteristics is advanced adenomas and I suggest this term be used.
2.  The purpose of dividing specimens into test and validation cohorts is not clear.  Although
is suggested that SMOC1 expression could be used as a biomarker, the data presented here is
descriptive rather than assessing a proposed predictive test.  I suggest the 2 cohorts be presented
as a single cohort
3.  The comparison of SMOC1 expression and clinicopathological characteristics is not
meaningful because SMOC1 expression varies with lesion type and the lesion type is associated
with clinicopathological characteristics as shown in Supp Tables 1 and 2.  To make this analysis
meaningful either clinicopathological variables should  be correlated with SMOC1 expression
within lesion types or a multivariate analysis should be performed.
Title: Downregulation of SMOC1 is associated with progression of colorectal traditional
serrated adenomas
Version: 1 Date: 22 Dec 2023
Reviewer's report:
The findings from this comprehensive study confirm the authors earlier work published in 2018
showing that SMOC1 is silenced by methylation in TSAs and also in conventional adenomas
and SSLs when they develop high grade dysplasia.  The methods are sound and the data clearly
presented.  There are some specific comments:
1.  The term high grade adenoma is confusing - the usual convention for adenomas with these
characteristics is advanced adenomas and I suggest this term be used.
2.  The purpose of dividing specimens into test and validation cohorts is not clear.  Although
is suggested that SMOC1 expression could be used as a biomarker, the data presented here is
descriptive rather than assessing a proposed predictive test.  I suggest the 2 cohorts be presented
as a single cohort
3.  The comparison of SMOC1 expression and clinicopathological characteristics is not
meaningful because SMOC1 expression varies with lesion type and the lesion type is associated
with clinicopathological characteristics as shown in Supp Tables 1 and 2.  To make this analysis
meaningful either clinicopathological variables should  be correlated with SMOC1 expression
within lesion types or a multivariate analysis should be performed.
Please review this paper.
user
Title: Downregulation of SMOC1 is associated with progression of colorectal traditional
serrated adenomas
Version: 1 Date: 22 Dec 2023
Reviewer's report:
The findings from this comprehensive study confirm the authors earlier work published in 2018
showing that SMOC1 is silenced by methylation in TSAs and also in conventional adenomas
and SSLs when they develop high grade dysplasia.  The methods are sound and the data clearly
presented.  There are some specific comments:
1.  The term high grade adenoma is confusing - the usual convention for adenomas with these
characteristics is advanced adenomas and I suggest this term be used.
2.  The purpose of dividing specimens into test and validation cohorts is not clear.  Although
is suggested that SMOC1 expression could be used as a biomarker, the data presented here is
descriptive rather than assessing a proposed predictive test.  I suggest the 2 cohorts be presented
as a single cohort
3.  The comparison of SMOC1 expression and clinicopathological characteristics is not
meaningful because SMOC1 expression varies with lesion type and the lesion type is associated
with clinicopathological characteristics as shown in Supp Tables 1 and 2.  To make this analysis
meaningful either clinicopathological variables should  be correlated with SMOC1 expression
within lesion types or a multivariate analysis should be performed.
assistant