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

• Published in: Cancer cell 2006-08, Vol.10 (2), p.99-111
• Main Authors: Budhu, Anuradha, Forgues, Marshonna, Ye, Qing-Hai, Jia, Hu-Liang, He, Ping, Zanetti, Krista A., Kammula, Udai S., Chen, Yidong, Qin, Lun-Xiu, Tang, Zhao-You, Wang, Xin Wei
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1535-6108; 1878-3686
• 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.