Title: Single-cell transcriptomic analysis reveals prognosis-related stromal signatures that
potentiate stratification of patients with extrahepatic cholangiocarcinoma
Version: 0 Date: 05 Jan 2025
Reviewer's report:
The authors proposed that stroma in eCCA can be classified using single cell transcriptome
analysis. The study appears to have been appropriately conducted. However, there are some
concerns with the present manuscript. Following points should be addressed.
Specific comments:
1. Figure legends: Please provide detailed explanations for each figure. Simply listing the title
of each result is insufficient for readers and reviewers.
2. Please provide continuous line numbers in the manuscript to facilitate the review process.
3. CAFs play crucial roles in both chemoresistance and cancer progression. Although the authors
cite one article regarding the link between CAFs and chemoresistance in page 20, this reviewer
recommends citing additional relevant studies. The following articles are suggested for citation.
https://doi.org/10.1038/s41416-024-02717-4
https://doi.org/10.1007/s10120-021-01174-9
4. Identification of epithelial cells and tumor cells: This reviewer cannot understand that how
they differentiate non-tumor epithelial cells and tumor cells since both cells express epithelial
cell markers. Additionally, proliferation markers are not helpful to differentiate them since non-
tumor epithelial cells can express high levels of proliferation markers as well as tumor cells.
5. Figure 7a and d: Are these stromal subgroups? While Group 2 and Group 3 are clear, Group
1 is unclear. What cell types are “proliferative”? The term may not be appropriate. Which cell
types are responsible for the upregulation of MYC in Figure 7d?
6. The association between gene expression profile/subtype in tumors in eCCA and stromal
subgroup: This reviewer thinks that tumors in eCCA also show different profiles/subtypes.
This reviewer suggests investigating the relationship between stromal subgroups (Groups 1-3
in Figure 7) and tumor subtypes. Does each stromal subgroup correspond to a specific tumor
subtype?
7. Figure 7c: Please refrain from showing the same data. Left upper plot show the same data
as the other plots.
8. Previous studies have shown that transcriptomic can identify molecular subtypes in tumors
as well as stromal subtypes. The authors should cite such papers. The following papers are
recommended for citation.
DOI: https://doi.org/10.1038/ng.3398
DOI: 10.1093/carcin/bgae056
Title: Single-cell transcriptomic analysis reveals prognosis-related stromal signatures that
potentiate stratification of patients with extrahepatic cholangiocarcinoma
Version: 0 Date: 05 Jan 2025
Reviewer's report:
The authors proposed that stroma in eCCA can be classified using single cell transcriptome
analysis. The study appears to have been appropriately conducted. However, there are some
concerns with the present manuscript. Following points should be addressed.
Specific comments:
1. Figure legends: Please provide detailed explanations for each figure. Simply listing the title
of each result is insufficient for readers and reviewers.
2. Please provide continuous line numbers in the manuscript to facilitate the review process.
3. CAFs play crucial roles in both chemoresistance and cancer progression. Although the authors
cite one article regarding the link between CAFs and chemoresistance in page 20, this reviewer
recommends citing additional relevant studies. The following articles are suggested for citation.
https://doi.org/10.1038/s41416-024-02717-4
https://doi.org/10.1007/s10120-021-01174-9
4. Identification of epithelial cells and tumor cells: This reviewer cannot understand that how
they differentiate non-tumor epithelial cells and tumor cells since both cells express epithelial
cell markers. Additionally, proliferation markers are not helpful to differentiate them since non-
tumor epithelial cells can express high levels of proliferation markers as well as tumor cells.
5. Figure 7a and d: Are these stromal subgroups? While Group 2 and Group 3 are clear, Group
1 is unclear. What cell types are “proliferative”? The term may not be appropriate. Which cell
types are responsible for the upregulation of MYC in Figure 7d?
6. The association between gene expression profile/subtype in tumors in eCCA and stromal
subgroup: This reviewer thinks that tumors in eCCA also show different profiles/subtypes.
This reviewer suggests investigating the relationship between stromal subgroups (Groups 1-3
in Figure 7) and tumor subtypes. Does each stromal subgroup correspond to a specific tumor
subtype?
7. Figure 7c: Please refrain from showing the same data. Left upper plot show the same data
as the other plots.
8. Previous studies have shown that transcriptomic can identify molecular subtypes in tumors
as well as stromal subtypes. The authors should cite such papers. The following papers are
recommended for citation.
DOI: https://doi.org/10.1038/ng.3398
DOI: 10.1093/carcin/bgae056
Please review this paper.
user
Title: Single-cell transcriptomic analysis reveals prognosis-related stromal signatures that
potentiate stratification of patients with extrahepatic cholangiocarcinoma
Version: 0 Date: 05 Jan 2025
Reviewer's report:
The authors proposed that stroma in eCCA can be classified using single cell transcriptome
analysis. The study appears to have been appropriately conducted. However, there are some
concerns with the present manuscript. Following points should be addressed.
Specific comments:
1. Figure legends: Please provide detailed explanations for each figure. Simply listing the title
of each result is insufficient for readers and reviewers.
2. Please provide continuous line numbers in the manuscript to facilitate the review process.
3. CAFs play crucial roles in both chemoresistance and cancer progression. Although the authors
cite one article regarding the link between CAFs and chemoresistance in page 20, this reviewer
recommends citing additional relevant studies. The following articles are suggested for citation.
https://doi.org/10.1038/s41416-024-02717-4
https://doi.org/10.1007/s10120-021-01174-9
4. Identification of epithelial cells and tumor cells: This reviewer cannot understand that how
they differentiate non-tumor epithelial cells and tumor cells since both cells express epithelial
cell markers. Additionally, proliferation markers are not helpful to differentiate them since non-
tumor epithelial cells can express high levels of proliferation markers as well as tumor cells.
5. Figure 7a and d: Are these stromal subgroups? While Group 2 and Group 3 are clear, Group
1 is unclear. What cell types are “proliferative”? The term may not be appropriate. Which cell
types are responsible for the upregulation of MYC in Figure 7d?
6. The association between gene expression profile/subtype in tumors in eCCA and stromal
subgroup: This reviewer thinks that tumors in eCCA also show different profiles/subtypes.
This reviewer suggests investigating the relationship between stromal subgroups (Groups 1-3
in Figure 7) and tumor subtypes. Does each stromal subgroup correspond to a specific tumor
subtype?
7. Figure 7c: Please refrain from showing the same data. Left upper plot show the same data
as the other plots.
8. Previous studies have shown that transcriptomic can identify molecular subtypes in tumors
as well as stromal subtypes. The authors should cite such papers. The following papers are
recommended for citation.
DOI: https://doi.org/10.1038/ng.3398
DOI: 10.1093/carcin/bgae056
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