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.
Keywords:
Allen and Lisa; Nestin; bilinear differentiation; clonal origin; intratumor heterogeneity; liver cancer; metastatic route; molecular subtype; phenotypic transition; single nucleus sequencing.
Copyright © 2019 Elsevier Inc. All rights reserved.
Publication types
-
Comparative Study
-
Multicenter Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Asia
-
Bile Duct Neoplasms / chemistry
-
Bile Duct Neoplasms / classification
-
Bile Duct Neoplasms / genetics*
-
Bile Duct Neoplasms / pathology
-
Biomarkers, Tumor / analysis
-
Biomarkers, Tumor / genetics*
-
Carcinoma, Hepatocellular / chemistry
-
Carcinoma, Hepatocellular / classification
-
Carcinoma, Hepatocellular / genetics*
-
Carcinoma, Hepatocellular / pathology
-
Cholangiocarcinoma / chemistry
-
Cholangiocarcinoma / classification
-
Cholangiocarcinoma / genetics*
-
Cholangiocarcinoma / pathology
-
Databases, Genetic
-
Female
-
Gene Expression Profiling*
-
Gene Expression Regulation, Neoplastic
-
Gene Regulatory Networks
-
Humans
-
Immunohistochemistry
-
Liver Neoplasms / chemistry
-
Liver Neoplasms / classification
-
Liver Neoplasms / genetics*
-
Liver Neoplasms / pathology
-
Male
-
Neoplasms, Complex and Mixed / chemistry
-
Neoplasms, Complex and Mixed / classification
-
Neoplasms, Complex and Mixed / genetics*
-
Neoplasms, Complex and Mixed / pathology
-
Nestin / analysis
-
Nestin / genetics*
-
Predictive Value of Tests
-
Prognosis
-
Transcriptome*
-
Up-Regulation
Substances
-
Biomarkers, Tumor
-
NES protein, human
-
Nestin