利用组织芯片技术研究酪氨酸蛋白激酶在肝癌组织中的表达及意义

目的 观察酪氨酸蛋白激酶ERK、P38、C-jun、JAK2、STAT3、STAT5在肝癌组织中的表达及相互关系,探讨酪氨酸蛋白激酶表达与肝癌病人临床特征之间的关系.方法 收集原发性肝癌手术切除标本30例,制作组织芯片,以肝硬化组织作对照,采用免疫组化SP法研究酪氨酸蛋白激酶ERK、P38、C-jun、JAK2、STAT3、STAT5在肝癌组织与肝硬化组织中的表达.结果 ERK、P38、C-jun、JAK2、STAT3、STAT5在肝癌组织中的表达平均光密度值分别为(0.220±0.033,0.174±0.024,0.183±0.064,0.192±0.044.0.197±0.078,0.181±0.066),显著高于肝硬化组(0.065±0.028,0.058±0.028,0.042±0.016,0.070±0.030,0.052±0.024,0.052±0.023,P＜0.01).ERK与C-jun、JAK2、STAT3、STAT5在肝癌组织中表达呈显著正相关,(P＜0.01或P＜0.05),与P38呈显著负相关(r=0.404,P＜0.05).JAK2的过度表达与肝癌组织中细胞的分化程度有关,在低分化肝癌组织中表达显著率高于高中分化肝癌组织.结论 MAPK和JAK-STAT通路的过度活化在肝癌发生发展过程中起重要作用,细胞信号转导系统失去正常的协调平衡可能是导致肿瘤发生的重要原因.

Determination of expression of tyrosine protein kinase in hepatocellular carcinoma by tissue chip

Objective To study the expression of tyrosine protein kinase in hepatocellular carcinoma(HCC)and observe the correlation between tyrosine protein kinase and clinical features.Methods A total of 30 cases with HCC were enrolled in this study.ERK,P38,C-jun,JAK2,STAT3 and STAT5 were detected by immunohistochemical method using tissue chip technology.Results The expression of ERK(0.220±0.033),P38(0.174±0.024),C-jun(0.183±0.064),JAK2(0.192±0.044),STAT3(0.197±0.078)and sTAT5(0.181±0.066)in HCC was significantly higher than that(0.065±0.028,0.058±0.028,0.042±0.016,0.070±0.030,0.052±0.024,0.052±0.023)in cirrhosis 1iver tissues(P＜0.01).There was significantly positive correlation of the expression between ERK,C-jun,JAK2,STAT3 and STAT5(P＜0.01 or P＜0.05).But the expression of P38 was negatively correlated with ERK in the HCC tissues(r=-0.404,P＜0.05).JAK2 had significant correlation with tumor differentiation.The expression of J AKz in stage Ⅲ was significantly higher than that in stage Ⅰ and Ⅱ cancer tissues.Conclusion There is important significance of the excessive activation of MAPK and JAK-STAT signaI transduction in hepatocellular carcinoma process.The unbalance of signal transduction might be one of the pathogenesis of tumor progress.