Title: Comparative Serum Imidazole Propionate Profiling in Colorectal Adenoma and Cancer
by UPLC-MS/MS
Version: 0 Date: 02 Apr 2025
Reviewer:  Makoto Ooi
Reviewer's report:
I am honored to be the reviewer of this paper.
The authors focused on the relationship between imidazolepropionic acid (ImP), a metabolite
produced from histidine by gut microbes, and CRC patients, and examined a new method to
detect serum ImP using ultra-performance liquid chromatography-tandem mass spectrometry
(UPLC-MS/MS) with 3-piperazin-1-ylpropionic acid as an internal standard (IS), and compared
ImP levels between patients with colorectal adenoma and colorectal cancer. The results
showed significant differences in serum ImP levels among Healthy Control Group (HC),
Conventional Colorectal Adenoma Group (CCA), Advanced Colorectal Adenoma Group
(ACA), and Colorectal Cancer Group (CRC), gradually increasing from healthy controls to
colorectal adenoma and CRC patients, and CRC patients had significantly higher ImP levels
compared to the other groups.
The results of this study are very meaningful and suggest that serum ImP levels may be a
biomarker for CRC.
To be convinced that serum ImP levels may be useful as a biomarker, the following points need
to be considered.
1) You said that ImP is a metabolite produced from histidine by intestinal microorganisms, but
is it produced in the intestinal tract or in the intestinal mucosa? If it is produced in the intestinal
tract, it is necessary to quantify the amount of ImP in the feces, and if it is produced in the tissues,
it is necessary to clarify the correlation with serum ImP concentration.
2) In relation to 1), in the discussion section, you mentioned the correlation other diseases with
serum ImP concentration. Is this serum ImP concentration? If so, please specify.
3) Previous studies have stated that there is a correlation between hypertension, diabetes, heart
failure, and chronic kidney disease and ImP concentration, so shouldn't Table 6 also consider
the presence or absence of these diseases?
4) Regarding the abstract and conclusion of the main text, since the majority of the research
content is about establishing an effective method for detecting serum ImP concentration,
shouldn't you first state that you have established a new method for detecting serum Imp
concentration, and then state the correlation between CRC and serum ImP levels?
5) In the induction section, you mentioned economics, so please explain how much more cost-
effective this method is than existing methods.
Title: Comparative Serum Imidazole Propionate Profiling in Colorectal Adenoma and Cancer
by UPLC-MS/MS
Version: 0 Date: 02 Apr 2025
Reviewer:  Makoto Ooi
Reviewer's report:
I am honored to be the reviewer of this paper.
The authors focused on the relationship between imidazolepropionic acid (ImP), a metabolite
produced from histidine by gut microbes, and CRC patients, and examined a new method to
detect serum ImP using ultra-performance liquid chromatography-tandem mass spectrometry
(UPLC-MS/MS) with 3-piperazin-1-ylpropionic acid as an internal standard (IS), and compared
ImP levels between patients with colorectal adenoma and colorectal cancer. The results
showed significant differences in serum ImP levels among Healthy Control Group (HC),
Conventional Colorectal Adenoma Group (CCA), Advanced Colorectal Adenoma Group
(ACA), and Colorectal Cancer Group (CRC), gradually increasing from healthy controls to
colorectal adenoma and CRC patients, and CRC patients had significantly higher ImP levels
compared to the other groups.
The results of this study are very meaningful and suggest that serum ImP levels may be a
biomarker for CRC.
To be convinced that serum ImP levels may be useful as a biomarker, the following points need
to be considered.
1) You said that ImP is a metabolite produced from histidine by intestinal microorganisms, but
is it produced in the intestinal tract or in the intestinal mucosa? If it is produced in the intestinal
tract, it is necessary to quantify the amount of ImP in the feces, and if it is produced in the tissues,
it is necessary to clarify the correlation with serum ImP concentration.
2) In relation to 1), in the discussion section, you mentioned the correlation other diseases with
serum ImP concentration. Is this serum ImP concentration? If so, please specify.
3) Previous studies have stated that there is a correlation between hypertension, diabetes, heart
failure, and chronic kidney disease and ImP concentration, so shouldn't Table 6 also consider
the presence or absence of these diseases?
4) Regarding the abstract and conclusion of the main text, since the majority of the research
content is about establishing an effective method for detecting serum ImP concentration,
shouldn't you first state that you have established a new method for detecting serum Imp
concentration, and then state the correlation between CRC and serum ImP levels?
5) In the induction section, you mentioned economics, so please explain how much more cost-
effective this method is than existing methods.
Please review this paper.
user
Title: Comparative Serum Imidazole Propionate Profiling in Colorectal Adenoma and Cancer
by UPLC-MS/MS
Version: 0 Date: 02 Apr 2025
Reviewer:  Makoto Ooi
Reviewer's report:
I am honored to be the reviewer of this paper.
The authors focused on the relationship between imidazolepropionic acid (ImP), a metabolite
produced from histidine by gut microbes, and CRC patients, and examined a new method to
detect serum ImP using ultra-performance liquid chromatography-tandem mass spectrometry
(UPLC-MS/MS) with 3-piperazin-1-ylpropionic acid as an internal standard (IS), and compared
ImP levels between patients with colorectal adenoma and colorectal cancer. The results
showed significant differences in serum ImP levels among Healthy Control Group (HC),
Conventional Colorectal Adenoma Group (CCA), Advanced Colorectal Adenoma Group
(ACA), and Colorectal Cancer Group (CRC), gradually increasing from healthy controls to
colorectal adenoma and CRC patients, and CRC patients had significantly higher ImP levels
compared to the other groups.
The results of this study are very meaningful and suggest that serum ImP levels may be a
biomarker for CRC.
To be convinced that serum ImP levels may be useful as a biomarker, the following points need
to be considered.
1) You said that ImP is a metabolite produced from histidine by intestinal microorganisms, but
is it produced in the intestinal tract or in the intestinal mucosa? If it is produced in the intestinal
tract, it is necessary to quantify the amount of ImP in the feces, and if it is produced in the tissues,
it is necessary to clarify the correlation with serum ImP concentration.
2) In relation to 1), in the discussion section, you mentioned the correlation other diseases with
serum ImP concentration. Is this serum ImP concentration? If so, please specify.
3) Previous studies have stated that there is a correlation between hypertension, diabetes, heart
failure, and chronic kidney disease and ImP concentration, so shouldn't Table 6 also consider
the presence or absence of these diseases?
4) Regarding the abstract and conclusion of the main text, since the majority of the research
content is about establishing an effective method for detecting serum ImP concentration,
shouldn't you first state that you have established a new method for detecting serum Imp
concentration, and then state the correlation between CRC and serum ImP levels?
5) In the induction section, you mentioned economics, so please explain how much more cost-
effective this method is than existing methods.
assistant