Title: Nanomolar EP4 receptor potency and expression of eicosanoid-related enzymes in normal
appearing colonic mucosa from patients with colorectal neoplasia
Version: 3 Date: 15 Feb 2022
Reviewer's report:
Review of “Nanomolar EP4 receptor potency and expression of eicosanoid-       related enzymes
in normal appearing colonic mucosa from patients with colorectal neoplasia” by Feddersen et al.
In this manuscript, the authors showed that biopsy samples from CRN react to prostaglandins
receptor agonists. In addition, mRNA expression of prostaglandin receptors and their related
gene was high in samples from CRN. This manuscript was already reviewed by another two
experts before this. And, authors well responded to comments from initial reviewers. However,
the data in this manuscript are too preliminary and not explored in sufficient detail to support
any clear conclusion. Some thoughts follow.
1. The major weakness of this study is that information of cell type in biopsy such as protein
expression or immune cell infiltration is missing. These differences may refer to these results.
Thus, it is hard to know the direct relationship between EP4 signaling and the pathogenesis of
CRN.
2. The information of inflammatory response in these biopsies is also missing. As the
authors described in the introduction, inflammation is the risk factor of CRC, information on
inflammation such as cytokine expression in biopsy is important to support the hypothesis of
this study.
3. How EC50 and SCC data were normalized? Protein levels or DNA contents in samples?
4. Ethnic information is missing
Title: Nanomolar EP4 receptor potency and expression of eicosanoid-related enzymes in normal
appearing colonic mucosa from patients with colorectal neoplasia
Version: 3 Date: 15 Feb 2022
Reviewer's report:
Review of “Nanomolar EP4 receptor potency and expression of eicosanoid-       related enzymes
in normal appearing colonic mucosa from patients with colorectal neoplasia” by Feddersen et al.
In this manuscript, the authors showed that biopsy samples from CRN react to prostaglandins
receptor agonists. In addition, mRNA expression of prostaglandin receptors and their related
gene was high in samples from CRN. This manuscript was already reviewed by another two
experts before this. And, authors well responded to comments from initial reviewers. However,
the data in this manuscript are too preliminary and not explored in sufficient detail to support
any clear conclusion. Some thoughts follow.
1. The major weakness of this study is that information of cell type in biopsy such as protein
expression or immune cell infiltration is missing. These differences may refer to these results.
Thus, it is hard to know the direct relationship between EP4 signaling and the pathogenesis of
CRN.
2. The information of inflammatory response in these biopsies is also missing. As the
authors described in the introduction, inflammation is the risk factor of CRC, information on
inflammation such as cytokine expression in biopsy is important to support the hypothesis of
this study.
3. How EC50 and SCC data were normalized? Protein levels or DNA contents in samples?
4. Ethnic information is missing
Please review this paper.
user
Title: Nanomolar EP4 receptor potency and expression of eicosanoid-related enzymes in normal
appearing colonic mucosa from patients with colorectal neoplasia
Version: 3 Date: 15 Feb 2022
Reviewer's report:
Review of “Nanomolar EP4 receptor potency and expression of eicosanoid-       related enzymes
in normal appearing colonic mucosa from patients with colorectal neoplasia” by Feddersen et al.
In this manuscript, the authors showed that biopsy samples from CRN react to prostaglandins
receptor agonists. In addition, mRNA expression of prostaglandin receptors and their related
gene was high in samples from CRN. This manuscript was already reviewed by another two
experts before this. And, authors well responded to comments from initial reviewers. However,
the data in this manuscript are too preliminary and not explored in sufficient detail to support
any clear conclusion. Some thoughts follow.
1. The major weakness of this study is that information of cell type in biopsy such as protein
expression or immune cell infiltration is missing. These differences may refer to these results.
Thus, it is hard to know the direct relationship between EP4 signaling and the pathogenesis of
CRN.
2. The information of inflammatory response in these biopsies is also missing. As the
authors described in the introduction, inflammation is the risk factor of CRC, information on
inflammation such as cytokine expression in biopsy is important to support the hypothesis of
this study.
3. How EC50 and SCC data were normalized? Protein levels or DNA contents in samples?
4. Ethnic information is missing
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