Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Cellular and Molecular Biology

Abstract #1445: Molecular and clinical characterization of hepatocellular carcinoma with progenitor cell markers

Augusto Villanueva, Yujin Hoshida, Derek Chiang, Pippa Newell, Kiat Lim, Laia Cabellos, Sara Toffanin, Swan Thung, Maria Fiel, Beatriz Minguez, Judit Peix, Victoria Tovar, Helena Cornella, Jordi Bruix, Sasan Roayaie, Myron Schwartz, Vincenzo Mazzaferro, Scott Friedman and Josep Llovet
Augusto Villanueva
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yujin Hoshida
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Derek Chiang
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pippa Newell
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kiat Lim
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laia Cabellos
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sara Toffanin
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Swan Thung
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria Fiel
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Beatriz Minguez
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Judit Peix
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Victoria Tovar
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Helena Cornella
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jordi Bruix
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sasan Roayaie
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Myron Schwartz
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincenzo Mazzaferro
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Scott Friedman
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Josep Llovet
IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; Broad Institute of Harvard and MIT, Cambridge, MA; Mount Sinai School of Medicine, New York, NY; National Cancer Institute, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published May 2009
  • Article
  • Info & Metrics
Loading
AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Abstract

Background: Recent reports support the role of cancer stem cells in the molecular pathogenesis of hepatocellular carcinoma (HCC), and suggest that progenitor cell markers categorize a subgroup of tumors with poorer prognosis. Objectives: (1) To explore the molecular alterations of a subgroup of human HCC with progenitor cell markers, and (2) to determine the clinical outcome of these tumors. Methods: A total of 326 human HCC samples were analyzed in two sets (n=77 HCV-related HCCs, and n=249 HCCs from patients with multiple etiologies). Progenitor cell markers (EpCAM, CK-19, c-KIT and CD133) were assessed by immunostaining, and correlated with annotated data from copy number changes (Affymetrix 500K Sty-array), gene expression (Affymetrix U133 Plus 2.0 and Taqman Probes) and signaling pathway activation (WNT-ßcatenin, EGFR, RAS and IGF-Akt-mTOR signaling). Dysregulated gene sets and specific signatures associated with progenitor cell markers were obtained using GSEA and SAMR packages, respectively. Correlations between CK19+ and EpCAM+ samples with clinico-pathological features and patient outcome were evaluated using Kaplan-Meier curves and Cox Proportional Hazard Test. Results: EpCAM and CK19 staining were present in 14/77 (18.1%) and 9/77 (11.9%) HCCs, respectively, whereas c-KIT was positive in no-tumoral cells in 15% of cases and CD133 was negative in all samples. CK19 and EpCAM staining were highly correlated (P=0.001), and significantly clustered in the proliferation subclass of the molecular classification of HCC (Chiang et al. Cancer Res 2008, P=0.01). EpCAM and CK19 were associated with p-AKT staining (P=0.01). GSEA revealed a significant dysregulation of cell cycle genes and PI3K signaling in CK19-positive samples. These samples were associated with higher AFP levels (P<0.01) and macrovascular invasion (P=0.04), whereas EpCAM-positive samples were enriched in multinodular tumors (38% vs 12%, P=0.03). The CK19 gene signature was present in 27% of the samples in the validation set, and was enriched in the proliferation class (P<0.0001). Regarding outcome correlation, CK19+ (HR: 4.1, p=0.004), satellites (HR: 2.3, p=0.0001) and multinodular HCCs (HR: 1.8, p=0.011) were independently associated with recurrence in the multivariate analysis of the validation set. Conclusion: There is a subgroup of HCC patients (15%) characterized by molecular features of progenitor cells. These tumors belong to the proliferation subgroup of the current molecular classification of HCC, are associated with macrovascular invasion and multinodularity and have a worse clinical outcome.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1445.

Footnotes

  • 100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

  • American Association for Cancer Research
Back to top
Cancer Research: 69 (9 Supplement)
May 2009
Volume 69, Issue 9 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Abstract #1445: Molecular and clinical characterization of hepatocellular carcinoma with progenitor cell markers
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Abstract #1445: Molecular and clinical characterization of hepatocellular carcinoma with progenitor cell markers
Augusto Villanueva, Yujin Hoshida, Derek Chiang, Pippa Newell, Kiat Lim, Laia Cabellos, Sara Toffanin, Swan Thung, Maria Fiel, Beatriz Minguez, Judit Peix, Victoria Tovar, Helena Cornella, Jordi Bruix, Sasan Roayaie, Myron Schwartz, Vincenzo Mazzaferro, Scott Friedman and Josep Llovet
Cancer Res May 1 2009 (69) (9 Supplement) 1445;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Abstract #1445: Molecular and clinical characterization of hepatocellular carcinoma with progenitor cell markers
Augusto Villanueva, Yujin Hoshida, Derek Chiang, Pippa Newell, Kiat Lim, Laia Cabellos, Sara Toffanin, Swan Thung, Maria Fiel, Beatriz Minguez, Judit Peix, Victoria Tovar, Helena Cornella, Jordi Bruix, Sasan Roayaie, Myron Schwartz, Vincenzo Mazzaferro, Scott Friedman and Josep Llovet
Cancer Res May 1 2009 (69) (9 Supplement) 1445;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Cellular and Molecular Biology

  • Abstract SY29-01: Functions of wild type and mutant p53
  • Abstract SY34-02: The impact of O2 availability on human cancer
  • Abstract SY19-01: Cell to cell variability in the responses of tumor cells to death ligands
Show more 3

Oncogenomics 2: Genome-wide mRNA Profiling of Cancer -- Poster Presentations - Proffered Abstracts

  • Abstract #1456: A genomic and transcriptional analysis of HPV-infected oropharyngeal head and neck squamous cell carcinoma.
  • Abstract #1453: Identification of interactive networks of gene expression associated with osteosarcoma oncogenesis by integrated molecular profiling of DNA methylation, copy number and gene expression
  • Abstract #1432: Genome-wide gene expression profiling in a novel "patient-like" rat model of intrahepatic cholangiocarcinoma progression closely mimicking the human disease
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement