BACKGROUND Liver fibrosis and hepatocellular carcinoma(HCC)are common adverse consequences of chronic liver injury.The interaction of various risk factors may cause them to happen.Identification of specific biomarkers...BACKGROUND Liver fibrosis and hepatocellular carcinoma(HCC)are common adverse consequences of chronic liver injury.The interaction of various risk factors may cause them to happen.Identification of specific biomarkers is of great significance for understanding the occurrence,development mechanisms,and determining the novel tools for diagnosis and treatment of both liver fibrosis and HCC.AIM To identify liver fibrosis-related core genes,we analyzed the differential expression pattern of core genes in liver fibrosis and HCC.METHODS Gene expression profiles of three datasets,GSE14323,GSE36411,and GSE89377,obtained from the Gene Expression Omnibus(GEO)database,were analyzed,and differentially expressed genes(DEGs)between patients with liver cirrhosis and healthy controls were identified by screening via R software packages and online tool for Venn diagrams.The WebGestalt online tool was used to identify DEGs enriched in biological processes,molecular functions,cellular components,and Kyoto Encyclopedia of Genes and Genomes pathways.The protein–protein interactions of DEGs were visualized using Cytoscape with STRING.Next,the expression pattern of core genes was analyzed using Western blot and immunohistochemistry in a carbon tetrachloride(CCl_(4))-induced liver cirrhosis mouse model and in patient liver samples.Finally,Kaplan-Meier curves were constructed using the Kaplan-Meier plotter online server.RESULTS Forty-five DEGs(43 upregulated and 2 downregulated genes)associated with liver cirrhosis were identified from three GEO datasets.Ten hub genes were identified,which were upregulated in liver cirrhosis.Western blot and immunohistochemical analyses of the three core genes,decorin(DCN),dermatopontin(DPT),and SRY-box transcription factor 9(SOX9),revealed that they were highly expressed in the CCl4-induced liver cirrhosis mouse model.The expression levels of DCN and SOX 9 were positively correlated with the degree of fibrosis,and SOX 9 level in HCC patients was significantly higher than that in fibrosis patients.However,high expression of DPT was observed only in patients with liver fibrosis,and its expression in HCC was low.The gene expression profiling interactive analysis server(GEPIA)showed that SOX9 was significantly upregulated whereas DCN and DPT were significantly downregulated in patients with HCC.In addition,the Kaplan-Meier curves showed that HCC patients with higher SOX9 expression had significantly lower 5-year survival rate,while patients with higher expression of DCN or DPT had significantly higher 5-year survival rates.CONCLUSION The expression levels of DCN,DPT,and SOX9 were positively correlated with the degree of liver fibrosis but showed different correlations with the 5-year survival rates of HCC patients.展开更多
文摘目的在体外用低氧无血清条件模拟缺血心肌微环境,探讨心肌细胞皮肤桥蛋白(DPT)表达的变化。方法以低氧无血清处理乳鼠心肌细胞0、6、12和24 h,用实时反转录聚合酶链式反应检测DPT mRNA的表达变化,用Western blot检测DPT的蛋白表达变化。用酶联免疫吸附实验(ELISA)证实低氧无血清处理乳鼠心肌细胞24 hDPT蛋白的表达变化。结果与0 h组相比,低氧无血清处理心肌细胞6、12、24 h DPT的mRNA和蛋白水平均显著升高(P<0.05)。用ELISA法也检测到低氧无血清处理心肌细胞24 h DPT的表达水平高于正常对照组(P<0.05)。结论低氧无血清可促进乳鼠心肌细胞DPT的表达,DPT可能在缺血缺氧引起的心室重构中发挥一定的作用。
基金Supported by the Beijing Natural Science Foundation,No.7222097Beijing Hospitals Authority the Digestive Medical Coordinated Development Center,No.XXZ0401+1 种基金National Natural Science Foundation of China,No.82000555 and No.81900547Beijing Municipal Science and Technology Commission,No.D171100003117005.
文摘BACKGROUND Liver fibrosis and hepatocellular carcinoma(HCC)are common adverse consequences of chronic liver injury.The interaction of various risk factors may cause them to happen.Identification of specific biomarkers is of great significance for understanding the occurrence,development mechanisms,and determining the novel tools for diagnosis and treatment of both liver fibrosis and HCC.AIM To identify liver fibrosis-related core genes,we analyzed the differential expression pattern of core genes in liver fibrosis and HCC.METHODS Gene expression profiles of three datasets,GSE14323,GSE36411,and GSE89377,obtained from the Gene Expression Omnibus(GEO)database,were analyzed,and differentially expressed genes(DEGs)between patients with liver cirrhosis and healthy controls were identified by screening via R software packages and online tool for Venn diagrams.The WebGestalt online tool was used to identify DEGs enriched in biological processes,molecular functions,cellular components,and Kyoto Encyclopedia of Genes and Genomes pathways.The protein–protein interactions of DEGs were visualized using Cytoscape with STRING.Next,the expression pattern of core genes was analyzed using Western blot and immunohistochemistry in a carbon tetrachloride(CCl_(4))-induced liver cirrhosis mouse model and in patient liver samples.Finally,Kaplan-Meier curves were constructed using the Kaplan-Meier plotter online server.RESULTS Forty-five DEGs(43 upregulated and 2 downregulated genes)associated with liver cirrhosis were identified from three GEO datasets.Ten hub genes were identified,which were upregulated in liver cirrhosis.Western blot and immunohistochemical analyses of the three core genes,decorin(DCN),dermatopontin(DPT),and SRY-box transcription factor 9(SOX9),revealed that they were highly expressed in the CCl4-induced liver cirrhosis mouse model.The expression levels of DCN and SOX 9 were positively correlated with the degree of fibrosis,and SOX 9 level in HCC patients was significantly higher than that in fibrosis patients.However,high expression of DPT was observed only in patients with liver fibrosis,and its expression in HCC was low.The gene expression profiling interactive analysis server(GEPIA)showed that SOX9 was significantly upregulated whereas DCN and DPT were significantly downregulated in patients with HCC.In addition,the Kaplan-Meier curves showed that HCC patients with higher SOX9 expression had significantly lower 5-year survival rate,while patients with higher expression of DCN or DPT had significantly higher 5-year survival rates.CONCLUSION The expression levels of DCN,DPT,and SOX9 were positively correlated with the degree of liver fibrosis but showed different correlations with the 5-year survival rates of HCC patients.
