Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment

Cancer Cell. 2006 Aug;10(2):99-111. doi: 10.1016/j.ccr.2006.06.016.


Hepatocellular carcinoma (HCC) is an aggressive malignancy mainly due to metastases or postsurgical recurrence. We postulate that metastases are influenced by the liver microenvironment. Here, we show that a unique inflammation/immune response-related signature is associated with noncancerous hepatic tissues from metastatic HCC patients. This signature is principally different from that of the tumor. A global Th1/Th2-like cytokine shift in the venous metastasis-associated liver microenvironment coincides with elevated expression of macrophage colony-stimulating factor (CSF1). Moreover, a refined 17 gene signature was validated as a superior predictor of HCC venous metastases in an independent cohort, when compared to other clinical prognostic parameters. We suggest that a predominant humoral cytokine profile occurs in the metastatic liver milieu and that a shift toward anti-inflammatory/immune-suppressive responses may promote HCC metastases.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / secondary
  • Cytokines / metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Hepatic Veins / pathology*
  • Humans
  • Immunity, Active
  • Liver / blood supply
  • Liver / immunology*
  • Liver / pathology
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local
  • Prognosis


  • Cytokines

Associated data

  • GEO/GSE5093
  • GEO/GSM114909
  • GEO/GSM114910
  • GEO/GSM114911
  • GEO/GSM114912
  • GEO/GSM114913
  • GEO/GSM114914
  • GEO/GSM114915
  • GEO/GSM114916
  • GEO/GSM114917
  • GEO/GSM114918
  • GEO/GSM114919
  • GEO/GSM114920
  • GEO/GSM114921
  • GEO/GSM114922
  • GEO/GSM114923
  • GEO/GSM114924
  • GEO/GSM114925
  • GEO/GSM114926
  • GEO/GSM114927
  • GEO/GSM114928