Cholangiocarcinoma (CCA), the second most prevalent liver cancer, encompasses a heterogenous group of bile duct malignancies. It predominantly arises from the epithelial cells lining the bile ducts termed cholangiocytes. Most CCA are highly desmoplastic adenocarcinomas, enmeshed in a tumour immune microenvironment. It exhibits a poor prognosis owing to its invasiveness and therapeutic resistance. Based on the anatomical location, CCA is classified into intrahepatic CCA (iCCA), perihilar CCA (pCCA) and distal CCA (dCCA). The epidemiology of these cancers varies worldwide. Infections with specific species of trematodes (flatworm parasites, commonly called flukes) are a major cause of CCA in regions where liver fluke infection is endemic. Moreover, iCCA can be further subdivided according to its morphology and cellular origin.1 2 The molecular heterogeneity of CCA reflects these differences. It displays genomic alterations in various pathways involved in cell cycle regulation, genomic stability and, notably, epigenetic modulation and chromatin remodelling, accompanied by considerable variation in the transcriptomic, methylomic, microRNA and proteomic levels. Jusakul et al performed a large-scale, integrative, multi-omics analysis and identified four prognostic clusters (Jusakul-Clusters) of CCA.3 Two of these were enriched for pCCA and dCCA, and one of them comprised exclusively of fluke-associated tumours. The cluster with the best prognosis consisted mainly of iCCA tumours, and was characterised by FGFR fusions, IDH1/2 …

中文翻译：

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增加胆管癌精准治疗的机会

胆管癌（CCA）是第二常见的肝癌，包括一组异质性胆管恶性肿瘤。它主要来自胆管内壁的上皮细胞，称为胆管细胞。大多数CCA是高度促纤维增生性腺癌，陷入肿瘤免疫微环境中。由于其侵袭性和治疗耐药性，其预后较差。根据解剖位置，CCA分为肝内CCA（iCCA）、肝门周围CCA（pCCA）和远端CCA（dCCA）。这些癌症的流行病学在世界范围内各不相同。在肝吸虫感染流行的地区，特定种类的吸虫（扁形虫寄生虫，通常称为吸虫）感染是导致 CCA 的主要原因。此外，iCCA还可以根据其形态和细胞起源进一步细分。1 2 CCA的分子异质性反映了这些差异。它显示了涉及细胞周期调控、基因组稳定性、特别是表观遗传调节和染色质重塑的各种途径的基因组改变，并伴随着转录组、甲基组、microRNA 和蛋白质组水平的相当大的变化。 Jusakul 等人进行了大规模、综合、多组学分析，并确定了 CCA 的四个预后簇（Jusakul 簇）。3 其中两个富含 pCCA 和 dCCA，其中一个完全由吸虫相关肿瘤组成。预后最好的簇主要由 iCCA 肿瘤组成，其特点是 FGFR 融合、IDH1/2……