Expression pattern of tumour-associated antigens in hepatocellular carcinoma: association with immune infiltration and disease progression

Br J Cancer. 2013 Aug 20;109(4):1031-9. doi: 10.1038/bjc.2013.390. Epub 2013 Jul 18.


Background: The distinct expression pattern of tumour-associated antigens (TAAs) might be a critical reason for the inefficacy of immunity-based treatments and heterogeneous postsurgical recovery in patients with solid tumours, including hepatocellular carcinoma (HCC). However, little is known about the clinical value of the coexpression patterns of multiple TAAs.

Methods: We determined the expression of multiple TAAs with identified immunogenicity (GPC3, AFP, SSX-2, NY-ESO-1, EpCAM, midkine) and the density of tumour-infiltrating immune cells by immunohistochemistry in a panel of 362 primary HCC patients. We evaluated the association between the TAAs, immune cell infiltration, clinicopathological parameters, and prognosis.

Results: Patients who coexpressed more TAAs had better prognosis (P<0.00001, overall survival). The integrated pattern of TAA was associated with good differentiation and small tumour size, and with more CD57(+) natural killer and CD20(+) B-cell infiltration (P<0.05). Multivariate Cox proportional hazards analysis identified the TAA index as an independent prognostic indicator (hazard ratio 0.625; 95% confidence interval 0.467-0.837; P=0.002), and could further predict patient prognosis in collaboration with local immune infiltration.

Conclusion: Our results could provide new evidence for the improvement of prognostic molecular signatures in HCC, and a novel rationale for patient enrolment in future immunotherapeutic trials and/or clinical treatments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / immunology*
  • B-Lymphocytes
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / mortality
  • Cell Adhesion Molecules / immunology
  • Cell Count
  • Disease Progression
  • Epithelial Cell Adhesion Molecule
  • Female
  • Glypicans / immunology
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Killer Cells, Natural
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / mortality
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Membrane Proteins / immunology
  • Middle Aged
  • Midkine
  • Neoplasm Proteins / immunology
  • Nerve Growth Factors / immunology
  • Prognosis
  • Proportional Hazards Models
  • Repressor Proteins / immunology
  • Young Adult
  • alpha-Fetoproteins / immunology


  • AFP protein, human
  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • GPC3 protein, human
  • Glypicans
  • MDK protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Nerve Growth Factors
  • Repressor Proteins
  • alpha-Fetoproteins
  • Midkine
  • synovial sarcoma X breakpoint proteins