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

By A. Budhu, M. Forgues, Q. Ye, H. Jia, P. He, Krista A. Zanetti, U. Kammula, Yidong Chen, L. Qin, Zhao-You Tang and 1 more. Cancer Cell, 2006

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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.

Subfields: Immunology, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/597bd41c113643bd922c888ddeae775c777a0f77

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Citations in the corpus

TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer (2007, background): “For example, genomic and gene expression analyses have identified key dysregulated signal transduction pathways involved in liver carcinogenesis (Thorgeirsson and Grisham, 2002; Ye et al., 2003; Budhu et al., 2006; Farazi and DePinho, 2006; Lee and Thorgeirsson, 2006).”
EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma. (2008, methodology): “A totalof 101 formal in-fixed and paraffin-embedded HCC samples (cohort 3) were used for immunohistochemical analysis, 7 of which were a part of cohort 1. Among the remaining 94 samples, 69 were also used in a recent study ( 12 ).”
Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1 (2009, background): “Furthermore, in a study of patients with hepatocellular carcinoma (HCC) (5), it was noted that an increased number of activated monocytes/M (HLA-DRhighCD68+ cells) in the liver was associated with progression CORRESPONDENCE Limin Zheng: zhenglm@mail.”
Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. (2008, background): “These immune cells may dictate the tumor microenvironment through a shift from inflammation/immune response to anti-inflammatory/immune-suppressive responses (Th1/Th2-like cytokine shift) and may be responsible in the metastatic liver milieu (Budhu et al., 2006).”
Cytokines and their relationship to the symptoms and outcome of cancer (2008, background): “A gene expression signature of 17 mainly cytokine-encoding genes isolated from non-cancerous liver tissue surrounding hepatocellular carcinoma, indicated that a switch from expression of T H 1 to T H 2 cytokines independently predicted tumour metastasis and recurrenc”
TGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progression (2010, background): “This concept is supported by recent findings that the immune/ inflammatory responses are reliable markers for predicting the clinical outcome in human hepatocellular carcinoma [85] and colorectal tumors [86].”
Focal Gains of Vascular Endothelial Growth Factor A and Molecular Classification of Hepatocellular Carcinoma (2008, background): “Intriguingly, an interleukin gene expression signature from the adjacent liver tissue has also been linked to higher rates of venous invasion and metastasis, pointing to the importance of tumor microenvironment in the genesis and intrahepatic dissemination of hepatocellular carcinoma (11).”
Inflammation and cancer: An ancient link with novel potentials (2007, background): “predominantly of humoral cytokines, promotes metastasis in hepatocellular carcinoma.(46) Likewise, a signature consisting of 11”