Title: Single-cell transcriptomic analysis reveals prognosis-related stromal signatures that
potentiate stratification of patients with extrahepatic cholangiocarcinoma
Version: 1 Date: 30 Jan 2025
Reviewer:  Hong-Yue Lai
Reviewer's report:
This study used single-cell RNA sequencing (scRNA-seq) to profile the tumor
microenvironment of extrahepatic cholangiocarcinoma (eCCA), focusing on stromal cell
heterogeneity and its impact on prognosis. By analyzing 37,498 individual cells from tumor and
adjacent normal tissues, the researchers identified key prognosis-related stromal subpopulations,
including proliferative hematopoietic progenitor-like cells (HPLCs), fibroblasts, Schwann cells,
mast cells, and regulatory T cells. Based on stromal signatures, eCCA tumors were classified
into three groups: (1) Proliferative, (2) Inflammatory and Fibrotic, and (3) Neuronal, with Group
3 showing the best prognosis. These findings highlight the significance of stromal components in
eCCA progression and suggest a new molecular classification system with potential therapeutic
implications.
This study is intriguing; however, several issues still need to be addressed.
Major concerns:
1.  The authors stated that single-cell transcriptomic analysis identified prognosis-related stromal
signatures; however, why were marker gene expression levels in bRNA-seq data used to
correlate stromal cell clusters with survival?
2. The cohort's background, including clinicopathological characteristics, treatment strategies,
and comorbidities that may influence patient survival, should be provided.
3. This study lacks experimental validation.
Title: Single-cell transcriptomic analysis reveals prognosis-related stromal signatures that
potentiate stratification of patients with extrahepatic cholangiocarcinoma
Version: 1 Date: 30 Jan 2025
Reviewer:  Hong-Yue Lai
Reviewer's report:
This study used single-cell RNA sequencing (scRNA-seq) to profile the tumor
microenvironment of extrahepatic cholangiocarcinoma (eCCA), focusing on stromal cell
heterogeneity and its impact on prognosis. By analyzing 37,498 individual cells from tumor and
adjacent normal tissues, the researchers identified key prognosis-related stromal subpopulations,
including proliferative hematopoietic progenitor-like cells (HPLCs), fibroblasts, Schwann cells,
mast cells, and regulatory T cells. Based on stromal signatures, eCCA tumors were classified
into three groups: (1) Proliferative, (2) Inflammatory and Fibrotic, and (3) Neuronal, with Group
3 showing the best prognosis. These findings highlight the significance of stromal components in
eCCA progression and suggest a new molecular classification system with potential therapeutic
implications.
This study is intriguing; however, several issues still need to be addressed.
Major concerns:
1.  The authors stated that single-cell transcriptomic analysis identified prognosis-related stromal
signatures; however, why were marker gene expression levels in bRNA-seq data used to
correlate stromal cell clusters with survival?
2. The cohort's background, including clinicopathological characteristics, treatment strategies,
and comorbidities that may influence patient survival, should be provided.
3. This study lacks experimental validation.
Please review this paper.
user
Title: Single-cell transcriptomic analysis reveals prognosis-related stromal signatures that
potentiate stratification of patients with extrahepatic cholangiocarcinoma
Version: 1 Date: 30 Jan 2025
Reviewer:  Hong-Yue Lai
Reviewer's report:
This study used single-cell RNA sequencing (scRNA-seq) to profile the tumor
microenvironment of extrahepatic cholangiocarcinoma (eCCA), focusing on stromal cell
heterogeneity and its impact on prognosis. By analyzing 37,498 individual cells from tumor and
adjacent normal tissues, the researchers identified key prognosis-related stromal subpopulations,
including proliferative hematopoietic progenitor-like cells (HPLCs), fibroblasts, Schwann cells,
mast cells, and regulatory T cells. Based on stromal signatures, eCCA tumors were classified
into three groups: (1) Proliferative, (2) Inflammatory and Fibrotic, and (3) Neuronal, with Group
3 showing the best prognosis. These findings highlight the significance of stromal components in
eCCA progression and suggest a new molecular classification system with potential therapeutic
implications.
This study is intriguing; however, several issues still need to be addressed.
Major concerns:
1.  The authors stated that single-cell transcriptomic analysis identified prognosis-related stromal
signatures; however, why were marker gene expression levels in bRNA-seq data used to
correlate stromal cell clusters with survival?
2. The cohort's background, including clinicopathological characteristics, treatment strategies,
and comorbidities that may influence patient survival, should be provided.
3. This study lacks experimental validation.
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