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

Anuradha Budhu, Marshonna Forgues, Qing Hai Ye, Hu Liang Jia, Ping He, Krista A. Zanetti, Udai S. Kammula, Yidong Chen, Lun Xiu Qin, Zhao You Tang, Xin Wei Wang

Research output: Contribution to journalArticlepeer-review

573 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)99-111
Number of pages13
JournalCancer Cell
Volume10
Issue number2
DOIs
StatePublished - Aug 2006

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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