目的:探讨DKK-1、DKK-2和人磷脂酰肌醇蛋白聚糖3(glypican3,GPC3)蛋白在肝细胞癌组织中的表达及临床意义。方法:采用组织芯片联合免疫组织化学法检测DKK-1、DKK-2和GPC3蛋白在10例正常肝、12例肝硬化、57例肝细胞癌及癌旁肝组织中的表...目的:探讨DKK-1、DKK-2和人磷脂酰肌醇蛋白聚糖3(glypican3,GPC3)蛋白在肝细胞癌组织中的表达及临床意义。方法:采用组织芯片联合免疫组织化学法检测DKK-1、DKK-2和GPC3蛋白在10例正常肝、12例肝硬化、57例肝细胞癌及癌旁肝组织中的表达差异,并分析其临床意义。结果:免疫组织化学检测结果发现,DKK-1和DKK-2在肝细胞癌组织中阳性染色率分别为59.65%(34/57)和57.89%(33/57);GPC3只在肝细胞癌组织中表达,其阳性染色率为47.37%(27/57),而在正常肝、肝硬化及癌旁肝组织中均呈阴性表达。DKK-1与DKK-2阳性表达之间存在密切相关性(χ2=0.570,P=0.000),DKK-2与GPC3阳性染色之间也存在相关性(χ2=0.272,P=0.041)。统计分析DKK-1、DKK-2及GPC3在肝细胞癌组织中阳性染色与肝癌患者性别、年龄、血清甲胎蛋白(α-fetoprotein,AFP)水平、乙肝表面抗原(hepatitis B surface antigen,HBsAg)、肿瘤大小、病理学分级、静脉浸润以及是否伴随肝硬化等的相关性,结果表明血清AFP水平与GPC3表达呈正相关(P=0.007),HBsAg与DKK-1表达呈正相关(P=0.037),DKK-1阳性染色与肝细胞癌组织分级存在相关性(P=0.014),与其他参数则无相关性。结论:GPC3在肝细胞癌组织的阳性染色率为47.37%,GPC3染色阴性的肝细胞癌组织中DKK-1和DKK-2双阳性染色率为40.00%,而GPC3(+)联合DKK-1(+)/DKK-2(+)/GPC3(-)可将肝细胞癌的免疫组织化学检出率提高至68.42%(39/57),降低肝癌免疫组织化学检测中的假阴性率。展开更多
Dysregulation of the Wnt pathway has been extensively studied in multiple diseases,including some angiogenic disorders.Wnt signaling activation is a major stimulator in pathological angiogenesis and thus,Wnt antagonis...Dysregulation of the Wnt pathway has been extensively studied in multiple diseases,including some angiogenic disorders.Wnt signaling activation is a major stimulator in pathological angiogenesis and thus,Wnt antagonists are believed to have therapeutic potential for neovascular disorders.Actually,some Wnt antagonists have been identified directly from the anti-angiogenic factor family.This review summarizes the recent progress toward understanding of the roles of Wnt pathway antagonists in angiogenic regulation and their mechanism of action,and exploring their therapeutic potential.展开更多
AIM:To investigate the promoter methylation status and mRNA expression of DKK-3 and WIF-1 gene in hepatocellular carcinoma(HCC).METHODS:DKK-3 and WIF-1 acted as Wnt-antagonists and tumor suppressors,but hypermethylati...AIM:To investigate the promoter methylation status and mRNA expression of DKK-3 and WIF-1 gene in hepatocellular carcinoma(HCC).METHODS:DKK-3 and WIF-1 acted as Wnt-antagonists and tumor suppressors,but hypermethylation of the gene promoter and low mRNA expression activated Wnt signaling aberrantly and induced the development of HCC.Methylation status of the DKK-3 and WIF-1 gene promoter was investigated using methylation specific polymerase chain reaction(PCR) in tumor and adjacent non-cancerous tissues from 33 HCC patients and 20 normal liver tissues served as control.The expression of DKK-3 and WIF-1 mRNA was also determined by real-time quantitative reverse transcriptase PCR.The relationship between methylation,mRNA expression,and clinical data,as well as methylation and mRNA expression of the two genes were analyzed.RESULTS:The methylation of DKK-3 and WIF-1 genes in HCC increased significantly compared with adjacent non-cancerous tissues and normal control tissues(χ2 =7.79,P < 0.05;χ2 = 4.89,P < 0.05),and no significant difference in methylation between adjacent non-cancerous tissues and normal control tissues was observed.In HCC tissues,significant differences in the DKK-3 promoter methylation were observed in age and cirrhosis,and significant differences of the WIF-1 promoter methylation were observed in HBsAg and cirrhosis.The average expression of DKK-3 mRNA in HCC and adjacent non-cancerous tissues was increased significantly compared with normal control tissues.The average expression of WIF-1 mRNA showed no significant difference among the three tissues.The mRNA expression of DKK-3 gene in HCC was decreased as the pathological grade increased.CONCLUSION:The aberrant promoter methylation and decreased expression of DKK-3 and WIF-1 may be an important mechanism in HCC,and may be a far-reaching significance in early diagnosis and therapy of HCC.展开更多
文摘目的:探讨DKK-1、DKK-2和人磷脂酰肌醇蛋白聚糖3(glypican3,GPC3)蛋白在肝细胞癌组织中的表达及临床意义。方法:采用组织芯片联合免疫组织化学法检测DKK-1、DKK-2和GPC3蛋白在10例正常肝、12例肝硬化、57例肝细胞癌及癌旁肝组织中的表达差异,并分析其临床意义。结果:免疫组织化学检测结果发现,DKK-1和DKK-2在肝细胞癌组织中阳性染色率分别为59.65%(34/57)和57.89%(33/57);GPC3只在肝细胞癌组织中表达,其阳性染色率为47.37%(27/57),而在正常肝、肝硬化及癌旁肝组织中均呈阴性表达。DKK-1与DKK-2阳性表达之间存在密切相关性(χ2=0.570,P=0.000),DKK-2与GPC3阳性染色之间也存在相关性(χ2=0.272,P=0.041)。统计分析DKK-1、DKK-2及GPC3在肝细胞癌组织中阳性染色与肝癌患者性别、年龄、血清甲胎蛋白(α-fetoprotein,AFP)水平、乙肝表面抗原(hepatitis B surface antigen,HBsAg)、肿瘤大小、病理学分级、静脉浸润以及是否伴随肝硬化等的相关性,结果表明血清AFP水平与GPC3表达呈正相关(P=0.007),HBsAg与DKK-1表达呈正相关(P=0.037),DKK-1阳性染色与肝细胞癌组织分级存在相关性(P=0.014),与其他参数则无相关性。结论:GPC3在肝细胞癌组织的阳性染色率为47.37%,GPC3染色阴性的肝细胞癌组织中DKK-1和DKK-2双阳性染色率为40.00%,而GPC3(+)联合DKK-1(+)/DKK-2(+)/GPC3(-)可将肝细胞癌的免疫组织化学检出率提高至68.42%(39/57),降低肝癌免疫组织化学检测中的假阴性率。
文摘Dysregulation of the Wnt pathway has been extensively studied in multiple diseases,including some angiogenic disorders.Wnt signaling activation is a major stimulator in pathological angiogenesis and thus,Wnt antagonists are believed to have therapeutic potential for neovascular disorders.Actually,some Wnt antagonists have been identified directly from the anti-angiogenic factor family.This review summarizes the recent progress toward understanding of the roles of Wnt pathway antagonists in angiogenic regulation and their mechanism of action,and exploring their therapeutic potential.
基金Supported by The Natural Science Fund of Educational Department of Anhui Province,No. 2006KJ094A
文摘AIM:To investigate the promoter methylation status and mRNA expression of DKK-3 and WIF-1 gene in hepatocellular carcinoma(HCC).METHODS:DKK-3 and WIF-1 acted as Wnt-antagonists and tumor suppressors,but hypermethylation of the gene promoter and low mRNA expression activated Wnt signaling aberrantly and induced the development of HCC.Methylation status of the DKK-3 and WIF-1 gene promoter was investigated using methylation specific polymerase chain reaction(PCR) in tumor and adjacent non-cancerous tissues from 33 HCC patients and 20 normal liver tissues served as control.The expression of DKK-3 and WIF-1 mRNA was also determined by real-time quantitative reverse transcriptase PCR.The relationship between methylation,mRNA expression,and clinical data,as well as methylation and mRNA expression of the two genes were analyzed.RESULTS:The methylation of DKK-3 and WIF-1 genes in HCC increased significantly compared with adjacent non-cancerous tissues and normal control tissues(χ2 =7.79,P < 0.05;χ2 = 4.89,P < 0.05),and no significant difference in methylation between adjacent non-cancerous tissues and normal control tissues was observed.In HCC tissues,significant differences in the DKK-3 promoter methylation were observed in age and cirrhosis,and significant differences of the WIF-1 promoter methylation were observed in HBsAg and cirrhosis.The average expression of DKK-3 mRNA in HCC and adjacent non-cancerous tissues was increased significantly compared with normal control tissues.The average expression of WIF-1 mRNA showed no significant difference among the three tissues.The mRNA expression of DKK-3 gene in HCC was decreased as the pathological grade increased.CONCLUSION:The aberrant promoter methylation and decreased expression of DKK-3 and WIF-1 may be an important mechanism in HCC,and may be a far-reaching significance in early diagnosis and therapy of HCC.
