热休克蛋白gp96表达水平与乙型肝炎病毒所致疾病进展之间存在显著相关性。
Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases.
作者信息
Zhu Xiao-Dong, Li Cheng-Lin, Lang Zhen-Wei, Gao George F, Tien Po
机构信息
Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Zhongguancun Beiyitiao, Beijing 100080, China.
出版信息
World J Gastroenterol. 2004 Apr 15;10(8):1141-5. doi: 10.3748/wjg.v10.i8.1141.
AIM
Gp96, also known as Grp94, is a member of heat shock protein (HSP) family and binds repertoires of peptides thereof eliciting peptide-specific T cell immune responses. It predominantly locates inside the endoplasmic reticulum (ER) with some cell surface expression in certain cancerous cells. Previous studies have shown that gp96 expression level was up-regulated in tumor cells, including hepatocellular carcinoma (HCC). However, relationship between the extent of gp96 expression and disease progression especially HBV-induced chronic infection, cirrhosis and hepatocellular carcinoma, has not been addressed before. As primary HCC can be induced and progressed from chronic hepatitis B virus (HBV) infection and HBV-induced cirrhosis, we designed an immunohistochemical experiment to test the correlation between gp96 expression level and HBV-induced disease progression, from chronic HBV infection, cirrhosis to HCC.
METHODS
We chose liver samples from different patients of hepatitis B virus induced diseases, including chronic hepatitis B (77 patients), cirrhosis (27 patients) and primary HCC (30 patients), to test the expression level of gp96 in different affected groups. Formalin-fixed, and paraffin-embedded liver tissues taken from these patients were immuno-stained by using an anti-gp96 monoclonal antibody for the expression level of gp96 protein in the sections. In addition, Western blotting of whole cell lysates derived from established human embryonic liver cell lines and several human HCC cell lines (Huh7, HepG2, SSMC-7721) was compared with the expression of gp96.
RESULTS
We found that the extent of elevated gp96 expression was significantly correlated with the disease progression, and was the highest in HCC patients, lowest in chronic HBV infection and was that of the cirrhosis in the middle.
CONCLUSION
Increased expression of gp96 might be used as a diagnostic or prognostic bio-marker for the HBV infection and HBV-induced diseases.
目的
Gp96，也称为Grp94，是热休克蛋白（HSP）家族的成员，可结合其肽库，引发肽特异性T细胞免疫反应。它主要位于内质网（ER）内，在某些癌细胞中有一些细胞表面表达。先前的研究表明，gp96表达水平在肿瘤细胞中上调，包括肝细胞癌（HCC）。然而，gp96表达程度与疾病进展尤其是HBV诱导的慢性感染、肝硬化和肝细胞癌之间的关系此前尚未得到探讨。由于原发性肝癌可由慢性乙型肝炎病毒（HBV）感染和HBV诱导的肝硬化引发和进展，我们设计了一项免疫组织化学实验，以测试gp96表达水平与HBV诱导的疾病进展（从慢性HBV感染、肝硬化到HCC）之间的相关性。
方法
我们选取了乙型肝炎病毒诱导疾病的不同患者的肝脏样本，包括慢性乙型肝炎（77例患者）、肝硬化（27例患者）和原发性肝癌（30例患者），以检测不同患病组中gp96的表达水平。使用抗gp96单克隆抗体对取自这些患者的福尔马林固定、石蜡包埋的肝组织进行免疫染色，以检测切片中gp96蛋白的表达水平。此外，将源自已建立的人胚胎肝细胞系和几种人肝癌细胞系（Huh7、HepG2、SSMC-7721）的全细胞裂解物的蛋白质印迹与gp96的表达进行比较。
结果
我们发现gp96表达升高的程度与疾病进展显著相关，在肝癌患者中最高，在慢性HBV感染患者中最低，肝硬化患者的gp96表达程度处于中间水平。
结论
gp96表达增加可能用作HBV感染和HBV诱导疾病的诊断或预后生物标志物。
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