Zeng Xiaokang, Ou Huohui, Zeng Chong, Liu Qingbo, Wang Weidong, Yao Jie
Medical Research Center, Shunde Hospital, Southern Medical University, Foshan, China.
Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University, Foshan, China.
Front Oncol. 2023 Jul 21;13:1175707. doi: 10.3389/fonc.2023.1175707. eCollection 2023.
Intrahepatic mucinous cholangiocarcinoma (IMCC) is a rare subtype of intrahepatic cholangiocarcinoma (IHCC). Limited data describe the genetic characteristics of IMCC and insights on its pathogenesis are lacking. Here, we employed a multi-omics approach to analyze somatic mutations, transcriptome, proteome and metabolome of tumor tissue obtained from a case of IMCC in order to clarify the pathogenesis of IMCC. A total of 54 somatic mutations were detected, including a G12D mutation in KRAS that is likely to be involved in the onset of IMCC. The genes consistently up-regulated at the transcription level and in the proteome were enriched for mucin and mucopolysaccharide biosynthesis, for cell cycle functions and for inflammatory signaling pathways. The consistently down-regulated genes were enriched in bile synthesis and fatty acid metabolism pathways. Further multi-omics analysis found that mucin synthesis by MUC4 and MUC16 was elevated by up-regulated expression of mesothelin (MSLN). Moreover, transcription factor ONECUT3 was identified that possibly activates the transcription of mucin and mucopolysaccharide biosynthesis in IMCC.
肝内黏液性胆管癌（IMCC）是肝内胆管癌（IHCC）的一种罕见亚型。关于IMCC基因特征的数据有限，且缺乏对其发病机制的深入了解。在此，我们采用多组学方法分析了一例IMCC患者肿瘤组织的体细胞突变、转录组、蛋白质组和代谢组，以阐明IMCC的发病机制。共检测到54个体细胞突变，其中KRAS基因的G12D突变可能与IMCC的发病有关。在转录水平和蛋白质组中持续上调的基因在黏蛋白和黏多糖生物合成、细胞周期功能及炎症信号通路方面富集。持续下调的基因在胆汁合成和脂肪酸代谢途径中富集。进一步的多组学分析发现，间皮素（MSLN）表达上调使MUC4和MUC16的黏蛋白合成增加。此外，还鉴定出转录因子ONECUT3，其可能激活IMCC中黏蛋白和黏多糖生物合成的转录。
