南方医科大学学报 ›› 2015, Vol. 35 ›› Issue (12): 1705-.

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髓样细胞触发受体-1与肝细胞癌发生和发展的相关性

李皖云,张娜,欧玉荣,周争光,赵福友,吴穷,杨燕   

  • 出版日期:2015-12-20 发布日期:2015-12-20

Correlation of triggering receptors expressed on myeloid cells-1 with the oncogenesis and
progression of hepatocellular carcinoma

  • Online:2015-12-20 Published:2015-12-20

摘要: 目的研究髓样细胞触发受体-1(TREM-1)在人肝细胞癌(HCC)发生发展过程中的表达及意义。方法应用免疫组化法检
测HCC 76例、肝硬化33例、肝炎30例、正常肝组织20例中TREM-1蛋白的表达及定位,并对该蛋白与HCC临床病理特征之间
的关系进行分析。进一步在体外使用人正常肝细胞LO2 和肝癌细胞SMMC-7721,采用RT-PCR 和Western blotting 法检测
TREM-1 mRNA及蛋白表达,以证实组织学结果。结果正常肝组织中TREM-1为阴性表达;肝炎、肝硬化和HCC组织中该蛋
白表达显著上调,阳性表达率分别为20.00%(6/30)、24.24%(8/33)和21.05%(16/76),但该3组间差异无统计学意义(χ2=0.195,
P=0.907)。与非癌肝组织(肝炎、肝硬化组织)相比,HCC组织中阳性表达的TREM-1 蛋白定位发生明显改变:非癌肝组织中
TREM-1 主要定位于肝细胞胞核中,偶见定位于细胞质;HCC组织中阳性表达的蛋白颗粒均位于癌细胞胞质,未见细胞核定
位。TREM-1蛋白与癌病理分级呈负相关(r=-0.261,P=0.023),而与年龄、性别、肿瘤大小、临床分期、肝病背景、淋巴结转移及
脉管癌栓无明显相关(均P>0.05)。细胞学实验显示LO2细胞有部分TREM-1 mRNA及蛋白表达,而SMMC-7721肝癌细胞该
指标明显上调。结论TREM-1蛋白的表达上调及在胞质中的异常定位可能与HCC发生发展相关。

Abstract: Objective To investigate the role of triggering receptors expressed on myeloid cells-1 (TREM-1) in the oncogenesis
and progression of hepatocellular carcinoma (HCC). Methods The expression and localization of TREM-1 were detected by
immunohistochemistry in 76 specimens of HCC, 33 specimens of liver cirrhosis, 30 specimens of hepatitis and 20 normal liver
tissues. The association between TREM-1 expression and the clinicopathologic parameters of HCC was analyzed. Human
normal hepatic cell line LO2 and HCC cell line SMMC-7721 were examined for TREM-1 expression pattern using RT-PCR and
Western blotting. Results All the normal liver samples showed negative expression of TREM-1 protein, which was significantly
up-regulated in the other 3 tissues. The positivity rates of TREM-1 expression were not significantly different between
hepatitis, cirrhosis and HCC tissues [20.00% (6/30), 24.24% (8/33), and 21.05% (16/76), respectively; χ2=0.195, P=0.907]. Different
from chronic hepatitis and liver cirrhosis tissues where TREM-1 expression was located mainly in the nucleus and occasionally
in the cytoplasm of the hepatocytes, HCC tissues showed a cellular localization of TREM-1 protein almost exclusively in the
cytoplasm. In HCC, TREM-1 expression was negatively correlated with the histological grade of the tumor (r=-0.261, P=0.023)
but not related with the patients’ age, gender, tumor size, clinical stage, pre-existing hepatitis and cirrhosis, lymph node
metastasis, or intrahepatic vascular embolism (all P>0.05). In the in vitro experiments, low levels of TREM-1 mRNA and protein
expressions were detected in LO2 cells line, but their expressions were markedly up-regulated in SMMC-7721 cells.
Conclusion Aberrant enhancement of the expression and cytoplasmic accumulation of TREM-1 may correlate closely with the
oncogenesis and progression of HCC.