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

Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes.
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肝细胞癌和肝内胆管癌的基因组和转录组分析揭示了不同的分子亚型

DOI:
10.1016/j.ccell.2019.04.007
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发表时间:
2019-06-10
期刊:
影响因子:
50.3
通讯作者:
Zhang N
Zhang N
中科院分区:
医学1区
文献类型:
--
作者:
Xue R;Chen L;Zhang C;Fujita M;Li R;Yan SM;Ong CK;Liao X;Gao Q;Sasagawa S;Li Y;Wang J;Guo H;Huang QT;Zhong Q;Tan J;Qi L;Gong W;Hong Z;Li M;Zhao J;Peng T;Lu Y;Lim KHT;Boot A;Ono A;Chayama K;Zhang Z;Rozen SG;Teh BT;Wang XW;Nakagawa H;Zeng MS;Bai F;Zhang N

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我们对133例合并的肝细胞和肝内胆管细胞癌(CHCC-ICC)进行了基因组和转录组学测序,包括单独的、合并的和混合的亚型。CHCC-ICC与肝细胞癌、肝内胆管细胞癌的综合比较发现,混合型和混合型是不同的亚型,具有不同的临床和分子特征。结合激光显微切割、癌细胞比例分析和单核测序,我们发现分离型CHCC-ICCs既有单克隆性起源,也有多克隆性起源,而混合型和混合型CHCC-ICCs均为单克隆性起源。值得注意的是,CHCC-ICCs中巢蛋白的表达显著增加,提示Nestin可作为诊断CHCC-ICC的生物标志物。我们的研究结果为研究CHCC-ICC提供了重要的生物学和临床方面的见解。
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.
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