title: Expression of TREM-1 in hepatic stellate cells and prognostic value in hepatitis B-related hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a typical inflammation-related malignancy characterized by high postoperative recurrence and metastasis. Although several inflammatory cells and inflammatory signatures have been linked to poor prognosis, the inflammation-associated molecular mechanisms of HCC development and progression are largely unknown. Here we show that triggering receptor expressed in myeloid cells (TREM)-1, a transmembrane receptor expressing in myeloid cells, was also expressed in tumor-activated hepatic stellate cells (HSCs) and associated with the aggressive behavior of HCC cells. Enzyme-linked immunosorbent assay was used to measure the expression levels of soluble TREM-1 (sTREM-1) in activated hepatic stellate cells supernatant and 92 preoperative and postoperative plasmas of patients with malignancy and/or benign liver tumor/disease, respectively. Expression levels of TREM-1 were assessed by immunohistochemistry in tissue microarray from 240 patients with HCC. As a result, increased secretion of sTREM-1 from activated HSCs was observed after co-culture with HCC cell lines (P < 0.001), and conditioned medium collected from activated HSCs/cancer associated myofibroblasts (CAMFs) with or without agonist/inhibitor of TREM-1 significantly changed the migratory ability of HCC cells. The levels of sTREM-1 were significantly higher in patients with HCC than those with benign liver tumors (P < 0.005). Peritumoral density of TREM-1 was shown to be an independent prognosis predictor according to univariate (P < 0.001 for both overall survival and time to recurrence) and multivariate analysis (P = 0.008 for overall survival; P = 0.005 for time to recurrence). Thus, these observations suggest that TREM-1 is related to the aggressive tumor behavior and has potential value as a prognostic factor for HCC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liao
authors.forename: Tai-Wei
authors.initials: TW
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Yi
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Li
authors.forename: Jia-Xing
authors.initials: JX
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Shi
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Cheng
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000821:virology; D002465:Cell Movement; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000737:chemistry; D005260:Female; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism; D011379:Prognosis; D011971:Receptors, Immunologic / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D017077:Culture Media, Conditioned; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha