Cancer Cell
Volume 35, Issue 6, 10 June 2019, Pages 932-947.e8
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Article
Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes

https://doi.org/10.1016/j.ccell.2019.04.007Get rights and content
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Highlights

  • We build the genomic and transcriptomic landscape of 133 cHCC-ICCs

  • Integrative genomic analysis reveals distinct cHCC-ICC subtypes

  • Both mono- and multiclonal origins of cHCC-ICC are identified

  • Nestin expression can serve as a biomarker for the diagnosis and prognosis of cHCC-ICC

Summary

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.

Keywords

liver cancer
molecular subtype
Allen and Lisa
bilinear differentiation
clonal origin
intratumor heterogeneity
phenotypic transition
metastatic route
single nucleus sequencing
Nestin

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19

These authors contributed equally

20

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