Clin Mol Hepatol.
2024 Oct;30(4):914-928. 10.3350/cmh.2024.0296.
Development and validation of a stromal-immune signature to predict prognosis in intrahepatic cholangiocarcinoma
- Ye YH1,2
- Xin HY1,2
- Li JL3
- Li N2
- Pan SY1,2
- Chen L1,2
- Pan JY2
- Hu ZQ1,2
- Wang PC1,2
- Luo CB1,2
- Sun RQ1,2
- Fan J1,2
- Zhou J1,2
- Zhou ZJ2
- Zhou SL
1,2
- Affiliations
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- 1Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China
- 2Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
- 3Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
- KMID: 2560093
- DOI: http://doi.org/10.3350/cmh.2024.0296
Abstract
- Background
Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC.
Patients and methods
We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time.
Results
We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort.
Conclusion
We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.
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