2型糖尿病合并肝癌患者癌组织RAGE、MKK7、JNK1表达变化及意义

摘要

目的 探讨晚期糖基化终末产物受体(RAGE)、丝裂原活化蛋白激酶激酶7(MKK7)及c-Jun氨基末端蛋白激酶1(JNK1)在2型糖尿病合并肝细胞癌(简称肝癌)患者癌组织中的表达及意义.方法 选择2型糖尿病合并肝癌患者18例(DMHC组)、单纯肝癌患者30例(HCC组),取两组手术切除的癌组织及相应的癌旁正常组织,采用Western blotting法检测其RAGE、MKK7及JNK1表达;分析两组癌组织RAGE、MKK7、JNK1表达与患者临床病理参数的关系,以及三者的相互关系.结果 DMHC组和HCC组癌组织RAGE、MKK7、JNK1的相对表达量均高于相应的癌旁正常组织(P均＜0.05),且DMHC组癌组织MKK7、JNK1的相对表达量均高于HCC组癌组织(P均＜0.05).HCC组低分化者RAGE、MKK7、JNK1的相对表达量均高于高分化者,DMHC组低分化者MKK7、JNK1的相对表达量均高于高分化者(P均＜0.05).DMHC组和HCC组癌组织RAGE、MKK7、JNK1表达均呈正相关(P均＜0.05).结论 RAGE表达升高可能参与肝癌的发生、发展;2型糖尿病患者MKK7、JNK1表达升高可能促进肝癌的发生、发展;MKK7和JNK1可能在一定水平上受RAGE的调控.%Objective To investigate the expression and significance of receptor for advanced glycation end products (RAGE),mitogen-activated protein kinase kinase 7 (MKK7) and c-Jun N-terminal protein kinase 1 (JNK1) in patients with type 2 diabetes mellitus complicated with hepatocellular carcinoma.Methods The resected cancer tissues and corresponding normal tissues were obtained from 18 patients with type 2 diabetes mellitus complicated with hepatocellular carcinoma (DMHC group) and 30 patients with simple hepatocellular carcinoma (HCC group).The expression of RAGE,MKK7 and JNK1 was detected by Western blotting.The relationships of RAGE,MKK7 and JNK1 expression in the two groups with the clinical and pathological parameters of the patients were analyzed as well as the relationship among RAGE,MKK7 and JNK1.Results The expression levels of RAGE,MKK7 and JNK1 were higher in the cancer tissues of both DMHC and HCC groups than those in their corresponding adjacent normal tissues (all P ＜ 0.05).Compared with the HCC group,MKK7 and JNK1 expression in the cancer tissues of the DMHC group was higher (all P ＜ 0.05).In the HCC group,the relative expression levels of RAGE,MKK7 and JNK1 in patients with poor differentiation were higher than those in patients with high differentiation,and in the DMHC group,the relative expression levels of MKK7 and JNK1 in patients with poor differentiation were higher than those in patients with high differentiation (all P ＜ 0.05).There was a positive correlation between the expression of RAGE,MKK7 and JNK1 in the DMHC group and HCC group (all P ＜ 0.05).Conclusions The increase of RAGE expression may be involved in the occurrence and development of hepatocellular carcinoma.The expression of MKK7 and JNK1 might promote the progress of hepatocellular carcinoma in hyperglycemic state.MKK7 and JNK1 may be regulated by RAGE to some extent.