Expression of TREM-1 in hepatic stellate cells and prognostic value in hepatitis B-related hepatocellular carcinoma
Expression of TREM-1 in hepatic stellate cells and prognostic value in hepatitis B-related hepatocellular carcinoma
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TREM-1在肝星状细胞中的表达及其在乙型肝炎相关肝细胞癌中的预后价值
DOI：
10.1111/j.1349-7006.2012.02273.x
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发表时间：
2012-06-01
期刊：
影响因子：
5.7
通讯作者：
Fan, Jia
中科院分区：
文献类型：
--
作者：
Liao, Rui;Sun, Tai-Wei;Fan, Jia
肝细胞癌（HCC）是一种典型的炎症相关性恶性肿瘤，术后复发转移率高。虽然一些炎症细胞和炎症信号与不良预后有关，但HCC发展和进展的炎症相关分子机制在很大程度上是未知的。在这里，我们表明，触发受体表达在髓样细胞（TREM）-1，一个跨膜受体表达在髓样细胞，也表达在肿瘤激活的肝星状细胞（HSC），并与肝癌细胞的侵袭行为。采用酶联免疫吸附试验（ELISA）检测92例肝脏恶性和/或良性肿瘤/疾病患者术前、术后血浆及活化肝星状细胞上清液中可溶性TREM-1（斯特雷姆-1）的表达水平。通过免疫组织化学方法在240例肝癌患者的组织微阵列中评估了TREM-1的表达水平。结果，在与HCC细胞系共培养后，观察到来自活化HSC的斯特雷姆-1分泌增加（P < 0.001），并且从活化HSC/癌症相关肌成纤维细胞（CAMF）收集的条件培养基（具有或不具有TREM-1的激动剂/抑制剂）显著改变HCC细胞的迁移能力。肝癌患者血清斯特雷姆-1水平显著高于良性肿瘤患者（P < 0.005）。根据单变量（总生存期和复发时间P < 0.001）和多变量分析（总生存期P = 0.008;复发时间P = 0.005），TREM-1的瘤周密度显示为独立的预后预测因子。因此，这些观察结果表明TREM-1与侵袭性肿瘤行为相关，并具有作为HCC预后因子的潜在价值。（Cancer Sci 2012; 103：984992）
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. (Cancer Sci 2012; 103: 984992)