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

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 hepati...

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Bibliographic Details
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
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Summary: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.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2006.06.016