Abstract:
Intrahepatic cholangiocarcinoma (ICC) 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 NF-kappa B and MAPK signaling pathways. Tumor cells were also differentially enriched for the IL-17 signaling pathway. There was less infiltration of SLC30A1+ CD8+ T cells expressing cytotoxic genes in MVI-associated ICC, whereas there was more infiltration of myeloid cells with attenuated expression of the MHC 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.
摘要:
肝内胆管癌(ICC)是一种罕见的疾病,预后不良,主要是由于早期复发和转移。这种状况的重要特征是微血管侵犯(MVI)。然而,目前基于成像的预测模型在这方面的疗效有限.本研究采用随机森林模型来构建MVI识别的预测模型,并揭示其生物学基础。单细胞转录组测序,整个外显子组测序,和蛋白质组测序。验证集合中预测模型的曲线下面积为0.93。进一步的分析表明,由于NF-κB和MAPK信号通路的改变,MVI相关的肿瘤细胞表现出与上皮-间质转化和脂质代谢相关的功能变化。肿瘤细胞也针对IL-17信号传导途径进行了差异富集。在MVI相关ICC中表达细胞毒性基因的SLC30A1+CD8+T细胞浸润较少,而MHCII途径表达减弱的骨髓细胞浸润更多。此外,MVI相关的细胞间通讯与SPP1-CD44和ANXA1-FPR1途径密切相关。这些发现产生了一个出色的预测模型和对MVI的新见解。