Single cell RNA sequencing to identify an Immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinoma
Abstract Immunogenic cell death (ICD) is crucial for cancer development and enhances the effectiveness of immunotherapy by triggering an adaptive immune response. However, the impact of ICD-related genes (ICDRGs) on iCCA progression and patient prognosis remains unclear. iCCA samples from The Cancer...
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Nature Portfolio
2025-07-01
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| author | Bowen Sha Fei Tong Qinghua Shu Miao Wu Liang Zhao Yufeng Zhang |
| author_facet | Bowen Sha Fei Tong Qinghua Shu Miao Wu Liang Zhao Yufeng Zhang |
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| description | Abstract Immunogenic cell death (ICD) is crucial for cancer development and enhances the effectiveness of immunotherapy by triggering an adaptive immune response. However, the impact of ICD-related genes (ICDRGs) on iCCA progression and patient prognosis remains unclear. iCCA samples from The Cancer Genome Atlas (TCGA) were categorized into two ICD-associated subtypes by consensus clustering, and patient prognosis in these subgroups was assessed. Single-cell RNA sequencing was conducted on viable cells from 8 iCCA patients to understand their transcriptomic profiles, heterogeneity, and immune microenvironment. Principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analysis were applied to identified 13 cell subpopulations. The gene set enrichment analysis (GSEA) was used to investigate pathway heterogeneity among these subpopulations. CellChat was employed for intercellular communication analysis. Pseudotime trajectory analyses with CytoTRACE and Monocle2 were used to explore differentiation trajectories and functional differences across various states. 30,485 single cells from human iCCA and normal tissues were sequenced, revealing two ICD-associated subtypes. The ICD-low subtype correlates with better clinical outcomes, whereas the ICD-high subtype is linked to increased immune cell infiltration and immune response signaling activity. Distinct biological functions and metabolic characteristics were observed in iCCA between high- and low-ICD groups. High infiltration of ICD-low subtype in iCCA is associated with poor prognosis, potentially through the ANXA-FPR pathway affecting macrophage proliferation and differentiation. Our study constructed an immunogenic cell death-related signature that can promise prognosis prediction and personalized medicine in iCCA. This finding might help guide clinicians for iCCA patients. |
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| institution | Kabale University |
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| spelling | doaj-art-2872cd3f9b0b48ac8efa14a7a3d1f6372025-08-20T03:45:28ZengNature PortfolioScientific Reports2045-23222025-07-0115111410.1038/s41598-025-08602-1Single cell RNA sequencing to identify an Immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinomaBowen Sha0Fei Tong1Qinghua Shu2Miao Wu3Liang Zhao4Yufeng Zhang5Department of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese MedicineDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Yangzhou UniversityDepartment of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese MedicineDepartment of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese MedicineDepartment of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese MedicineDepartment of Hepatopancreatobiliary Surgery, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese MedicineAbstract Immunogenic cell death (ICD) is crucial for cancer development and enhances the effectiveness of immunotherapy by triggering an adaptive immune response. However, the impact of ICD-related genes (ICDRGs) on iCCA progression and patient prognosis remains unclear. iCCA samples from The Cancer Genome Atlas (TCGA) were categorized into two ICD-associated subtypes by consensus clustering, and patient prognosis in these subgroups was assessed. Single-cell RNA sequencing was conducted on viable cells from 8 iCCA patients to understand their transcriptomic profiles, heterogeneity, and immune microenvironment. Principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analysis were applied to identified 13 cell subpopulations. The gene set enrichment analysis (GSEA) was used to investigate pathway heterogeneity among these subpopulations. CellChat was employed for intercellular communication analysis. Pseudotime trajectory analyses with CytoTRACE and Monocle2 were used to explore differentiation trajectories and functional differences across various states. 30,485 single cells from human iCCA and normal tissues were sequenced, revealing two ICD-associated subtypes. The ICD-low subtype correlates with better clinical outcomes, whereas the ICD-high subtype is linked to increased immune cell infiltration and immune response signaling activity. Distinct biological functions and metabolic characteristics were observed in iCCA between high- and low-ICD groups. High infiltration of ICD-low subtype in iCCA is associated with poor prognosis, potentially through the ANXA-FPR pathway affecting macrophage proliferation and differentiation. Our study constructed an immunogenic cell death-related signature that can promise prognosis prediction and personalized medicine in iCCA. This finding might help guide clinicians for iCCA patients.https://doi.org/10.1038/s41598-025-08602-1Immunogenic cell deathIntrahepatic cholangiocarcinomaTumor microenvironmentPrognostic biomarkerSingle-cell RNA sequencing |
| spellingShingle | Bowen Sha Fei Tong Qinghua Shu Miao Wu Liang Zhao Yufeng Zhang Single cell RNA sequencing to identify an Immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinoma Scientific Reports Immunogenic cell death Intrahepatic cholangiocarcinoma Tumor microenvironment Prognostic biomarker Single-cell RNA sequencing |
| title | Single cell RNA sequencing to identify an Immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinoma |
| title_full | Single cell RNA sequencing to identify an Immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinoma |
| title_fullStr | Single cell RNA sequencing to identify an Immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinoma |
| title_full_unstemmed | Single cell RNA sequencing to identify an Immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinoma |
| title_short | Single cell RNA sequencing to identify an Immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinoma |
| title_sort | single cell rna sequencing to identify an immunogenic cell death related prognostic signature in intrahepatic cholangiocarcinoma |
| topic | Immunogenic cell death Intrahepatic cholangiocarcinoma Tumor microenvironment Prognostic biomarker Single-cell RNA sequencing |
| url | https://doi.org/10.1038/s41598-025-08602-1 |
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