Reviewer's report
Title:Gene Expression Profiling of Laterally Spreading Tumors
Version:2Date:3 March 2015
Reviewer: Jordi Camps
Reviewer's report:
In the present manuscript, Minemura and colleagues attempted to generate the
trancriptional profiling of colorectal laterally spreading tumors (LST) using
PCR-based array analysis by comparing 17 adenomas, 12 carcinomas and 12
pedunculated adenomas as a control. Immunohistochemistry results confirmed
and validated that overexpression of BCL2L1 is associated with laterally
spreading tumors, and potentially indicate worse prognosis. Functionally, the
authors attempted to inversely correlate the expression of the anti-tumor BCL2L1
with the presence of apoptosis in tissue sections. Thus the authors conclude that
BCL2L1 is upregulated and blocks apoptosis in laterally spreading tumors.
The manuscript is well structured and very straightforward; however, there are
some suggestions this reviewer would like to make in order to give some strength
to the author's conclusions.
Major revisions:
1. Some of the conclusions the authors make are only observational so there are
some statements that there should be downsized.
2. The inverse correlation between expression of BCL2L1 and apoptosis is highly
speculative unless some functional assays are performed. There is no biological
rationality to claim that the inverse relation between expression of BCL2L1 and
apoptosis happens specifically in LTS.
3. If possible, the correlation between mRNA and the protein should be
performed in the same set of samples.
4. The methodological description of the immunohistochemistry should include
each dilution factor utilized for each antibody.
5. In Figure 1, some L-Can cluster within the groups of adenomas, both LTS and
non-LTS. Given the fact that cancers should actually be the most well separated
entities in the hierarchical clustering, the authors should attempt to find an
explanation about their results.
6. Is the overexpression of BCL2L1 a marker of high-grade dysplasia in LTS only
or it is also true for other tumor subtypes?
7. The results of the qRT-PCR would be much easier to follow by the reader if
they are presented in a plot (e.g. box plot).
8. Although it is mentioned by the authors in the Discussion, it would be
informative to know whether BCL2L1 upregulated cells are Ki-67 positive. This
could give some insights in the mechanism of action.
9. The rationale as to why the authors dropped off the follow-up of TNFRSF25 is
not clear.
Minor revisions:
1. The name of the genes must be in italics.
2. Last paragraph in the abstract needs to be rewritten.
3. In Line 251 "claim" should "replace" declare.
4. In Line 258 "to" should replace "with".
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I do not have competing interests.
Reviewer's report
Title:Gene Expression Profiling of Laterally Spreading Tumors
Version:2Date:3 March 2015
Reviewer: Jordi Camps
Reviewer's report:
In the present manuscript, Minemura and colleagues attempted to generate the
trancriptional profiling of colorectal laterally spreading tumors (LST) using
PCR-based array analysis by comparing 17 adenomas, 12 carcinomas and 12
pedunculated adenomas as a control. Immunohistochemistry results confirmed
and validated that overexpression of BCL2L1 is associated with laterally
spreading tumors, and potentially indicate worse prognosis. Functionally, the
authors attempted to inversely correlate the expression of the anti-tumor BCL2L1
with the presence of apoptosis in tissue sections. Thus the authors conclude that
BCL2L1 is upregulated and blocks apoptosis in laterally spreading tumors.
The manuscript is well structured and very straightforward; however, there are
some suggestions this reviewer would like to make in order to give some strength
to the author's conclusions.
Major revisions:
1. Some of the conclusions the authors make are only observational so there are
some statements that there should be downsized.
2. The inverse correlation between expression of BCL2L1 and apoptosis is highly
speculative unless some functional assays are performed. There is no biological
rationality to claim that the inverse relation between expression of BCL2L1 and
apoptosis happens specifically in LTS.
3. If possible, the correlation between mRNA and the protein should be
performed in the same set of samples.
4. The methodological description of the immunohistochemistry should include
each dilution factor utilized for each antibody.
5. In Figure 1, some L-Can cluster within the groups of adenomas, both LTS and
non-LTS. Given the fact that cancers should actually be the most well separated
entities in the hierarchical clustering, the authors should attempt to find an
explanation about their results.
6. Is the overexpression of BCL2L1 a marker of high-grade dysplasia in LTS only
or it is also true for other tumor subtypes?
7. The results of the qRT-PCR would be much easier to follow by the reader if
they are presented in a plot (e.g. box plot).
8. Although it is mentioned by the authors in the Discussion, it would be
informative to know whether BCL2L1 upregulated cells are Ki-67 positive. This
could give some insights in the mechanism of action.
9. The rationale as to why the authors dropped off the follow-up of TNFRSF25 is
not clear.
Minor revisions:
1. The name of the genes must be in italics.
2. Last paragraph in the abstract needs to be rewritten.
3. In Line 251 "claim" should "replace" declare.
4. In Line 258 "to" should replace "with".
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I do not have competing interests.
Please review this paper.
user
Reviewer's report
Title:Gene Expression Profiling of Laterally Spreading Tumors
Version:2Date:3 March 2015
Reviewer: Jordi Camps
Reviewer's report:
In the present manuscript, Minemura and colleagues attempted to generate the
trancriptional profiling of colorectal laterally spreading tumors (LST) using
PCR-based array analysis by comparing 17 adenomas, 12 carcinomas and 12
pedunculated adenomas as a control. Immunohistochemistry results confirmed
and validated that overexpression of BCL2L1 is associated with laterally
spreading tumors, and potentially indicate worse prognosis. Functionally, the
authors attempted to inversely correlate the expression of the anti-tumor BCL2L1
with the presence of apoptosis in tissue sections. Thus the authors conclude that
BCL2L1 is upregulated and blocks apoptosis in laterally spreading tumors.
The manuscript is well structured and very straightforward; however, there are
some suggestions this reviewer would like to make in order to give some strength
to the author's conclusions.
Major revisions:
1. Some of the conclusions the authors make are only observational so there are
some statements that there should be downsized.
2. The inverse correlation between expression of BCL2L1 and apoptosis is highly
speculative unless some functional assays are performed. There is no biological
rationality to claim that the inverse relation between expression of BCL2L1 and
apoptosis happens specifically in LTS.
3. If possible, the correlation between mRNA and the protein should be
performed in the same set of samples.
4. The methodological description of the immunohistochemistry should include
each dilution factor utilized for each antibody.
5. In Figure 1, some L-Can cluster within the groups of adenomas, both LTS and
non-LTS. Given the fact that cancers should actually be the most well separated
entities in the hierarchical clustering, the authors should attempt to find an
explanation about their results.
6. Is the overexpression of BCL2L1 a marker of high-grade dysplasia in LTS only
or it is also true for other tumor subtypes?
7. The results of the qRT-PCR would be much easier to follow by the reader if
they are presented in a plot (e.g. box plot).
8. Although it is mentioned by the authors in the Discussion, it would be
informative to know whether BCL2L1 upregulated cells are Ki-67 positive. This
could give some insights in the mechanism of action.
9. The rationale as to why the authors dropped off the follow-up of TNFRSF25 is
not clear.
Minor revisions:
1. The name of the genes must be in italics.
2. Last paragraph in the abstract needs to be rewritten.
3. In Line 251 "claim" should "replace" declare.
4. In Line 258 "to" should replace "with".
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I do not have competing interests.
assistant