北京大学白凡/张宁团队经过课题组成员不懈努力，通过分析基因组和转录组特征，揭示了混合型肝癌的不同分子亚型。该研究于2019年5月23日发表于《Cancer Cell》杂志上。

研究小组收集了133例合并肝细胞癌和肝内胆管癌(cHCC-ICC)的混合型肝癌样本，包括分离型、结合型和混合亚型三种病理亚型，并对样本进行了基因组测序和转录组测序。将cHCC-ICC与单纯性肝细胞癌、肝内胆管癌进行综合比较，发现结合型和混合型cHCC-ICCs确属不同的疾病亚型，具有不同的临床和分子特征。通过激光显微切割获得肿瘤细胞，并对其进行癌细胞组分分析和单核酸序列分析，课题组发现了分离型cHCC-ICCs亚型中同时存在癌细胞单克隆和多克隆起源，而结合型和混合型cHCC-ICCs中的癌细胞均为单克隆起源。值得注意的是，cHCC-ICCs中Nestin蛋白的表达显著升高，提示Nestin蛋白有望作为诊断cHCC-ICC的生物标志物。研究结果为未来研究cHCC-ICC提供了重要的生物学和临床依据。

据介绍，混合型肝癌兼具肝细胞癌和胆管细胞癌两种成分，是预后最差的一类肝癌疾病。

附：英文原文

Title: Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes

Author: Ruidong Xue, Lu Chen, Chong Zhang, Mu-Sheng Zeng, Fan Bai, Ning Zhang

Issue&Volume: Jun 10, 2019 Volume 35Issue 6

Abstract: We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes. Integrative comparison of cHCC-ICC with hepatocellular carcinoma and intrahepatic cholangiocarcinoma revealed that combined and mixed type cHCC-ICCs are distinct subtypes with different clinical and molecular features. Integrating laser microdissection, cancer cell fraction analysis, and single nucleus sequencing, we revealed both mono- and multiclonal origins in the separate type cHCC-ICCs, whereas combined and mixed type cHCC-ICCs were all monoclonal origin. Notably, cHCC-ICCs showed significantly higher expression of Nestin, suggesting Nestin may serve as a biomarker for diagnosing cHCC-ICC. Our results provide important biological and clinical insights into cHCC-ICC.

DOI: https://doi.org/10.1016/j.ccell.2019.04.007

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30202-8