Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, 25 Taiping Road, Luzhou 646000, Sichuan Province, China.
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, and Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, 79 Qingchun Road, Hangzhou 310000, Zhejiang Province, China.
Carcinogenesis. 2024 Oct 10;45(10):721-734. doi: 10.1093/carcin/bgae052.
Intrahepatic cholangiocarcinoma is a rare disease associated with a poor prognosis, primarily due to early recurrence and metastasis. An important feature of this condition is microvascular invasion (MVI). However, current predictive models based on imaging have limited efficacy in this regard. This study employed a random forest model to construct a predictive model for MVI identification and uncover its biological basis. Single-cell transcriptome sequencing, whole exome sequencing, and proteome sequencing were performed. The area under the curve of the prediction model in the validation set was 0.93. Further analysis indicated that MVI-associated tumor cells exhibited functional changes related to epithelial-mesenchymal transition and lipid metabolism due to alterations in the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. Tumor cells were also differentially enriched for the interleukin-17 signaling pathway. There was less infiltration of SLC30A1+ CD8+ T cells expressing cytotoxic genes in MVI-associated intrahepatic cholangiocarcinoma, whereas there was more infiltration of myeloid cells with attenuated expression of the major histocompatibility complex II pathway. Additionally, MVI-associated intercellular communication was closely related to the SPP1-CD44 and ANXA1-FPR1 pathways. These findings resulted in a brilliant predictive model and fresh insights into MVI.
肝内胆管癌是一种预后不良的罕见疾病,主要由于早期复发和转移。这种疾病的一个重要特征是微血管侵犯(MVI)。然而,目前基于影像学的预测模型在这方面的效果有限。本研究采用随机森林模型构建了用于 MVI 识别的预测模型,并揭示了其生物学基础。进行了单细胞转录组测序、全外显子组测序和蛋白质组测序。验证集中预测模型的曲线下面积为 0.93。进一步分析表明,由于核因子-κB 和丝裂原活化蛋白激酶信号通路的改变,MVI 相关肿瘤细胞表现出与上皮-间充质转化和脂质代谢相关的功能变化。肿瘤细胞也在白细胞介素-17 信号通路中差异富集。在 MVI 相关的肝内胆管癌中,表达细胞毒性基因的 SLC30A1+CD8+T 细胞浸润较少,而表达主要组织相容性复合体 II 途径减弱的髓样细胞浸润较多。此外,MVI 相关的细胞间通讯与 SPP1-CD44 和 ANXA1-FPR1 途径密切相关。这些发现导致了一个出色的预测模型,并为 MVI 提供了新的见解。