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 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.
Budhu
Anuradha
A
Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
Forgues
Marshonna
M
Ye
Qing-Hai
QH
Jia
Hu-Liang
HL
He
Ping
P
Zanetti
Krista A
KA
Kammula
Udai S
US
Chen
Yidong
Y
Qin
Lun-Xiu
LX
Tang
Zhao-You
ZY
Wang
Xin Wei
XW
D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000276:immunology* / Q000556:secondary; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006503:Hepatic Veins / Q000473:pathology*; D006801:Humans; D007110:Immunity, Active; D008099:Liver / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D008113:Liver Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011379:Prognosis
D016207:Cytokines