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Cited by 296Cholangiocarcinoma and Gallbladder Cancer StudiesHepatocellular Carcinoma Treatment and PrognosisCancer Genomics and Diagnostics

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

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Xue, Ruidong, Chen, Lu, Zhang, Chong, Fujita, Masashi, Li, Ruoyan, Yan, Shu-Mei, Ong, Choon Kiat, Liao, Xiwen +27 more·2019·Cancer Cell
DOI 10.1016/j.ccell.2019.04.007PMC PMC8317046
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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.

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  • In patients with HCC, chromosomal amplifications including PROX1 are associated with increased survival.

    “in patients with HCC, high PROX1 expression or chromosomal amplifications including PROX1 were both associated with increased survival25–32”

    From Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis (2025) · cites this paper as [31]

    The Results section on copy-number alterations reports amplifications of several genes, but does not mention PROX1 or link those amplifications to survival. The Transcriptomic Comparison section reports survival differences between molecular clusters, not by PROX1 amplification. Searches for PROX1 and for its amplification–survival association found no supporting passage in our copy; page numbers were unavailable. (LLM, conf=0.75)

    Experimental — accuracy not yet measured

  • In patients with HCC, high PROX1 expression is associated with increased survival.

    “in patients with HCC, high PROX1 expression or chromosomal amplifications including PROX1 were both associated with increased survival25–32”

    From Active repression of cell fate plasticity by PROX1 safeguards hepatocyte identity and prevents liver tumorigenesis (2025) · cites this paper as [31]

    The Results sections on Transcriptomic Comparison and Nestin Expression report survival associations for molecular clusters and Nestin, respectively; page numbers are unavailable in our copy. Searches for PROX1, PROX1 expression and survival, and PROX1 amplification and prognosis returned no passage linking PROX1 expression to survival in HCC. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

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Authors
Xue, R., Chen, L., Zhang, C., Fujita, M., Li, R., Yan, S.-M., Ong, C. K., Liao, X., Gao, Q., Sasagawa, S., Li, Y., Wang, J., Guo, H., Huang, Q.-T., Zhong, Q., Tan, J., Qi, L., Gong, W., Hong, Z., Li, M., Zhao, J., Peng, T., Lu, Y., Lim, K. H. T., Boot, A., Ono, A., Chayama, K., Zhang, Z., Rozen, S. G., Teh, B. T., Wang, X. W., Nakagawa, H., Zeng, M.-S., Bai, F., & Zhang, N.
Affiliations
  • Peking University (CN)
  • Tianjin Medical University Cancer Institute and Hospital (CN)
  • RIKEN Center for Integrative Medical Sciences (JP)
  • National Cancer Centre Singapore (SG)
  • First Affiliated Hospital of GuangXi Medical University (CN)
  • Fudan University (CN)
  • Sun Yat-sen University Cancer Center (CN)
  • 302 Military Hospital of China (CN)
  • Singapore General Hospital (SG)
  • Duke-NUS Medical School (SG)
  • Hiroshima University (JP)
  • National Cancer Institute (US)
Corresponding author
  • Nakagawa, Hidewaki
  • Zeng, Mu-Sheng
  • Bai, Fan
  • Zhang, Ning
ORCID
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2019-06
Volume
35
Issue
6
Pages
932-947.e8
ISSN
1535-6108 (ISSN-L)
DOI
10.1016/j.ccell.2019.04.007
PMC
PMC8317046
OpenAlex
W2945946815
Cited by
296
References
7
Citations by year
2026: 27 · 2025: 34 · 2024: 42 · 2023: 57 · 2022: 48 · 2021: 49 · 2020: 28 · 2019: 11
FWCI
31.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NCC
  • Scientific Research Seed Fund (2018SF039)
  • JSPS (18H04049)
  • National Key Research and Development Program (2016YFC0900102)
  • National Science and Technology (2018ZX10302205)
  • Guangdong Province Key Research and Development Program (2019B020226002)
  • National Natural Science Foundation of China (81802813, 81520108022, 81830090, 81661128009, 31671421, 81472683)
Topics
  • Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
molecular subtypes, tumor origin, monoclonal origin, nestin, biomarkers, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, single-nucleus sequencing, laser microdissection
MeSH terms
Asia, Bile Duct Neoplasms, Female, Carcinoma, Hepatocellular, Humans, Immunohistochemistry, Liver Neoplasms, Male, Predictive Value of Tests, Prognosis, Biomarkers, Tumor, Up-Regulation, Gene Expression Regulation, Neoplastic, Neoplasms, Complex and Mixed, Cholangiocarcinoma, Gene Expression Profiling, Databases, Genetic, Gene Regulatory Networks, Transcriptome, Nestin

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