title: Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment.
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.
authors.affiliation: Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Budhu
authors.forename: Marshonna
authors.initials: M
authors.lastname: Forgues
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Ye
authors.forename: Hu-Liang
authors.initials: HL
authors.lastname: Jia
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Krista A
authors.initials: KA
authors.lastname: Zanetti
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Xin Wei
authors.initials: XW
authors.lastname: Wang
mesh_terms: 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
chemical_list: D016207:Cytokines