Title: Linoleic acid pathway disturbance contributing to potential cancerization of intrahepatic
bile duct stones into intrahepatic cholangiocarcinoma
Version: 0 Date: 02 Apr 2022
Reviewer's report:
This research work is a study of intrahepatic cholangiocarcinoma (ICC) and intrahepatic bile
duct stones (IBDS) using GC-MS based metabolomics study on the pathological tissue. I
appreciate your research rationale and method used in this study. You propose that the linoleic
acid pathway may play role in cholangiocarcinoma carcinogenesis.
I have questions and comments as follows.
Major issues:
1. It's not clear about tissue representative, how do you select and confirm representative areas
for ICC tumor tissue, para-carcinoma tissue, and IBDS pathological tissue for study? Did the
authors confirm the tissue samples, ICC and IBDS cases, with pathologists in the specimens
selected for GC-MS?
2. Do you have any cases of ICC + IBDS in the same patient? How do you analyze them? If you
have that, the dataset could be analyzed in 5 subcategories; ICC tissue (cases without stones),
ICC tissue (cases ICC with IBDS), para-carcinoma bile duct tissue (cases ICC with IBDS), para-
carcinoma bile duct tissue (cases ICC without IBDS), and normal bile duct tissue (cases IBDS
without cancer).
3. Did you find any precancerous lesions like biliary intraepithelial neoplasia (BilIN) in your
cases? Is it present in para-carcinoma bile duct tissue?
4. Regrading exclusion criteria; "history of any metabolic diseases" should be defined more. Is
the list of metabolic diseases include obesity or dyslipidemia?
5. Regarding the surrogate marker for cholangiocarcinoma, the authors state GGT and AFP were
indicators of cancerization markers for hepatic carcinoma and disease characteristics of IBDS.
Could you please explain more and give some references.
6. Could you please explain the outlier of concentration of 9,12-octadecadienoic acid among
ICC-T.
Minor issues:
1. The word "metabonomics" in Scheme 1, is it correct?
2. The font sizes of (A) and (B) should be adjusted in Figure 2.
3. Also, the legend "ICC-L" in Figure 2 is not corresponding to the text.
Title: Linoleic acid pathway disturbance contributing to potential cancerization of intrahepatic
bile duct stones into intrahepatic cholangiocarcinoma
Version: 0 Date: 02 Apr 2022
Reviewer's report:
This research work is a study of intrahepatic cholangiocarcinoma (ICC) and intrahepatic bile
duct stones (IBDS) using GC-MS based metabolomics study on the pathological tissue. I
appreciate your research rationale and method used in this study. You propose that the linoleic
acid pathway may play role in cholangiocarcinoma carcinogenesis.
I have questions and comments as follows.
Major issues:
1. It's not clear about tissue representative, how do you select and confirm representative areas
for ICC tumor tissue, para-carcinoma tissue, and IBDS pathological tissue for study? Did the
authors confirm the tissue samples, ICC and IBDS cases, with pathologists in the specimens
selected for GC-MS?
2. Do you have any cases of ICC + IBDS in the same patient? How do you analyze them? If you
have that, the dataset could be analyzed in 5 subcategories; ICC tissue (cases without stones),
ICC tissue (cases ICC with IBDS), para-carcinoma bile duct tissue (cases ICC with IBDS), para-
carcinoma bile duct tissue (cases ICC without IBDS), and normal bile duct tissue (cases IBDS
without cancer).
3. Did you find any precancerous lesions like biliary intraepithelial neoplasia (BilIN) in your
cases? Is it present in para-carcinoma bile duct tissue?
4. Regrading exclusion criteria; "history of any metabolic diseases" should be defined more. Is
the list of metabolic diseases include obesity or dyslipidemia?
5. Regarding the surrogate marker for cholangiocarcinoma, the authors state GGT and AFP were
indicators of cancerization markers for hepatic carcinoma and disease characteristics of IBDS.
Could you please explain more and give some references.
6. Could you please explain the outlier of concentration of 9,12-octadecadienoic acid among
ICC-T.
Minor issues:
1. The word "metabonomics" in Scheme 1, is it correct?
2. The font sizes of (A) and (B) should be adjusted in Figure 2.
3. Also, the legend "ICC-L" in Figure 2 is not corresponding to the text.
Please review this paper.
user
Title: Linoleic acid pathway disturbance contributing to potential cancerization of intrahepatic
bile duct stones into intrahepatic cholangiocarcinoma
Version: 0 Date: 02 Apr 2022
Reviewer's report:
This research work is a study of intrahepatic cholangiocarcinoma (ICC) and intrahepatic bile
duct stones (IBDS) using GC-MS based metabolomics study on the pathological tissue. I
appreciate your research rationale and method used in this study. You propose that the linoleic
acid pathway may play role in cholangiocarcinoma carcinogenesis.
I have questions and comments as follows.
Major issues:
1. It's not clear about tissue representative, how do you select and confirm representative areas
for ICC tumor tissue, para-carcinoma tissue, and IBDS pathological tissue for study? Did the
authors confirm the tissue samples, ICC and IBDS cases, with pathologists in the specimens
selected for GC-MS?
2. Do you have any cases of ICC + IBDS in the same patient? How do you analyze them? If you
have that, the dataset could be analyzed in 5 subcategories; ICC tissue (cases without stones),
ICC tissue (cases ICC with IBDS), para-carcinoma bile duct tissue (cases ICC with IBDS), para-
carcinoma bile duct tissue (cases ICC without IBDS), and normal bile duct tissue (cases IBDS
without cancer).
3. Did you find any precancerous lesions like biliary intraepithelial neoplasia (BilIN) in your
cases? Is it present in para-carcinoma bile duct tissue?
4. Regrading exclusion criteria; "history of any metabolic diseases" should be defined more. Is
the list of metabolic diseases include obesity or dyslipidemia?
5. Regarding the surrogate marker for cholangiocarcinoma, the authors state GGT and AFP were
indicators of cancerization markers for hepatic carcinoma and disease characteristics of IBDS.
Could you please explain more and give some references.
6. Could you please explain the outlier of concentration of 9,12-octadecadienoic acid among
ICC-T.
Minor issues:
1. The word "metabonomics" in Scheme 1, is it correct?
2. The font sizes of (A) and (B) should be adjusted in Figure 2.
3. Also, the legend "ICC-L" in Figure 2 is not corresponding to the text.
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