DUSP6在肝细胞肝癌中的表达与MAPK信号通路及临床病理学特征相关性研究

摘要

Objective: This study aims to investigate the expression of dual specificity phosphatase 6 (DUSP6) in hepatocellular carcinoma (HCC) and the correlation of DUSP6 with the mitogen-activated protein kinase signaling pathway and clinicopathological characteristics. Methods: The expressions of DUSP6, p-ERK, p-JNK, p-P38α, CyclinD1, and Ki-67 were assessed via imrnunohistochemistry in tissue microarrays containing paired tumor and peritumoral liver tissue from 305 patients who had undergone hepatectomy for HCC. Statistical analysis was performed to assess the relationship between DUSP6 and others or the clinicopathologic factors. Results: The DUSP6 expression was significantly higher in the tumor tissue compared with that in the peritumor or normal liver tissue (P＜0.001). The expression of p-ERK, p-JNK, and Ki-67 was significantly different between the tumor and the peritumor (P＜0.001). Spearman correlation analysis demonstrated that the DUSP6 expression positively correlated with p-ERK, CyclinDl, and Ki-67 (Γ=0.179, P＜0.01; r=0.213, P<0.01; γ=0.137, P＜0.05). DUSP6 expression was significantly associated with hepatitis B and liver cirrhosis history for the group with relative tumor expression (P=0.034 and P=0.044, respectively). Conclusion: DUSP6 expression in HCC was overexpressed compared with that in peritumor or normal liver tissue. DUSP6 may provide a negative feedback regulation to the p-ERK overexpression in HCC. The DUSP6 overexpression may have a role in regulating the cell cycle and promoting the proliferative activity of HCC.%目的:探讨DUSP6在肝细胞肝癌(hepatocellular carcinoma,HCC)中的表达及其与MAPK信号通路和临床病理学特征相关性.方法:查询复旦大学附属中山医院肝癌研究所2005年1月至2006年12月HCC临床病理资料数据库,筛选出305例HCC制作组织芯片,免疫组化检测DUSP6、p-ERK、p-JNK、p-P380α、CyclinD1和Ki-67表达,将以上结果同临床病理学特征进行统计学相关性分析.结果:HCC肿瘤组织、癌旁组织和正常肝组织DUSP6表达存在显著性差异(P＜0.001)；p-ERK、p-JNK和Ki-67肿瘤组织与癌旁组织表达存在显著性差异(P＜0.001).Spearman相关性分析,在HCC肿瘤组织中DUSP6和p-ERK,CyclinD1及Ki-67的表达呈显著正相关(r=0.179,P＜0.01；r=0.213,P＜0.01；r=0.137,P＜0.05).相对癌旁,各组肿瘤组织DUSP6表达、有乙肝和肝硬化病史者不同分组间均存在显著性差异(P＜0.05).结论:DUSP6在HCC中肿瘤组织较癌旁组织和正常肝组织过表达,DUSP6对p-ERK过表达可能起负反馈调节作用.DUSP6过表达可能与HCC细胞周期调节及促进肿瘤增殖活性有关.