临床肝胆病杂志2017，Vol.33Issue(10)：1949-1954,6.DOI:10.3969/j.issn.1001-5256.2017.10.020
葡萄糖调节蛋白78调控乙型肝炎相关性肝细胞癌患者线粒体生成蛋白的表达及临床分析
Glucose-regulated protein 78 regulates the expression of mitochondrial genesis proteins in HBV-related hepatocellular carcinoma: a clinical analysis
摘要
Abstract
Objective To investigate the expression of glucose-regulated protein 78 (GRP78) in HBV-related hepatocellular carcinoma (HBV-HCC) and its association with clinicopathological features,as well as its regulatory effect on mitochondrial genesis proteins in hepatoma cells,and to provide a basis for new strategies for the prevention and treatment of HCC.Methods Tissue samples were collected from 54 patients with HBV-HCC,and immunohistochemistry and Western blot were used to measure the expression of GRP78,Lon,TFAM,and cytochrome C oxidase Ⅳ (COX Ⅳ).The expression of GRP78 in hepatoma cells was interfered by siRNA,and then the expression of GRP78,Lon,mitochondrial transcription factor A (TFAM),and COX Ⅳ was measured.Quantitative real-time PCR was used to measure the level of mitochondrial DNA (mtDNA) in clinical specimens and HCC cells after GRP78 expression was interfered with.A statistical analysis was performed for clinical and experimental data.The t-test was used for comparison of continuous data between groups,the Fisher's exact test was used for comparison of categorical data between groups,and the Kaplan-Meier method was used for survival analysis.Results Compared with the adjacent tissues,HBV-HCC tissues had significantly higher expression of GRP78 and Lon (t =9.135 and 5.523,both P ＜0.0001) and significantly lower expression of the mitochondrial genesis proteins TFAM and COX Ⅳ and mtDNA level (t =2.765,4.260,and 12.280,P =0.011,＜0.001,and ＜0.001).There were significant increases in the expression of the mitochondrial genesis proteins TFAM and COX Ⅳ and mtDNA level after the interference with GRP78 expression in hepatoma cells (all P ＜ 0.05).There were significant differences in the expression of GRP78 between patients with different numbers of tumors,patients with and without portal vein tumor thrombus,and patients with different tumor stages (P =0.016,0.003,and 0.045).The patients with low GRP78 expression had significantly longer overall survival and recurrence-free survival after surgery than those with high GRP78 expression (x2 =5.006 and 4.995,P =0.025 and 0.026).Conclusion GRP78 has a potential regulatory effect on mitochondrial genesis and maintenance and has important clinical guiding significance in establishing new strategies for the prevention and treatment of HCC.关键词
癌,肝细胞/肝炎病毒,乙型/线粒体蛋白质类Key words
carcinoma,hepatocellular/hepatitis B virus/mitochondrial proteins分类
医药卫生引用本文复制引用
李亚萍,王媛,翟嵩,贾晓黎,张欣,潘国英,杨颖..葡萄糖调节蛋白78调控乙型肝炎相关性肝细胞癌患者线粒体生成蛋白的表达及临床分析[J].临床肝胆病杂志,2017,33(10):1949-1954,6.基金项目
国家自然科学基金资助(81500453) （81500453）
