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基质-免疫特征的建立和验证，以预测肝内胆管癌的预后。

Development and validation of a stromal-immune signature to predict prognosis in intrahepatic cholangiocarcinoma.

机构信息

Department of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, China.

Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Clin Mol Hepatol. 2024 Oct;30(4):914-928. doi: 10.3350/cmh.2024.0296. Epub 2024 Aug 6.

DOI:10.3350/cmh.2024.0296
PMID:39103994
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11540385/
Abstract

BACKGROUNDS/AIMS: 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.

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.

摘要

背景/目的：肝内胆管癌（ICC）是一种高度促结缔组织增生性肿瘤，即使在根治性切除后预后也很差。我们研究了 ICC 基质的组成与免疫细胞浸润之间的关系，并旨在开发一种基质-免疫特征来预测接受手术治疗的 ICC 患者的预后。

方法

我们招募了 359 名 ICC 患者，并进行免疫组织化学检测以检测α-平滑肌肌动蛋白（α-SMA）、CD3、CD4、CD8、Foxp3、CD68 和 CD66b。苯胺用于染色胶原沉积。进行生存分析以检测这些标志物的预后价值。应用递归分区的离散时间生存树来定义具有明确预后价值的基质-免疫特征。我们根据免疫细胞亚群和基质组成描绘了一个综合的基质-免疫特征，以区分具有不同无复发生存（RFS）和总生存（OS）时间的亚组。

结果

根据α-SMA 和胶原的分布，我们将 ICC 基质组成定义为四种主要模式：休眠（α-SMAlow/collagenhigh）、纤维生成（α-SMAhigh/collagenhigh）、惰性（α-SMAlow/collagenlow）和纤维溶解（α-SMAhigh/collagenlow）。基质类型的特点是免疫细胞浸润的模式不同。我们将患者分为六类。以高 CD8 表达和休眠基质为特征的 Class I 显示最长的 RFS 和 OS，而以低 CD8 表达和高 CD66b 表达为特征的 Class VI 显示最短的 RFS 和 OS。整合的基质-免疫特征在验证队列中得到了验证。

结论

我们开发并验证了一种基质-免疫特征来预测接受手术治疗的 ICC 患者的预后。这些发现为 ICC 中基质-免疫反应提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9c/11540385/c223471c6fa6/cmh-2024-0296f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9c/11540385/15e7de5e4f7d/cmh-2024-0296f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9c/11540385/51b0bec50902/cmh-2024-0296f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9c/11540385/a6fef23c2afd/cmh-2024-0296f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9c/11540385/c223471c6fa6/cmh-2024-0296f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9c/11540385/15e7de5e4f7d/cmh-2024-0296f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9c/11540385/51b0bec50902/cmh-2024-0296f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9c/11540385/a6fef23c2afd/cmh-2024-0296f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b9c/11540385/c223471c6fa6/cmh-2024-0296f4.jpg

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