肾细胞癌组织中的组蛋白甲基化酶表达及其临床意义  

Expression of SET8 in renal cell carcinoma tissue and its clinical significance

作　　者：韦秀望[1] 易晓明[2] 唐朝朋[2] 徐振宇[2] 梁建波[1] 蓝志相[1] 周文泉[2] 

机构地区：[1]广西壮族自治区人民医院泌尿外科,南宁医学硕士530021 [2]南京军区南京总医院泌尿外科,南京210002

出　　处：《医学研究生学报》2015年第10期1048-1052,共5页Journal of Medical Postgraduates

基　　金：国家自然基金项目(81372742)

摘　　要：目的肾细胞癌(renal cell carcinoma,RCC)的发生发展是多因素作用下的复杂过程,DNA异常甲基化、组蛋白修饰和Wnt信号通路等影响着RCC的发生发展。文中旨在研究组蛋白甲基化酶(histone methylase SET domain containing 8,SET8)在RCC组织中的表达,探讨其与Wnt信号通路的关联及在RCC中的作用机制及临床意义。方法采用单纯随机抽样法选取2010年至2012年广西壮族自治区人民医院的RCC标本50例,运用HE染色和免疫组化染色(二级计分法)及通过滴加兔抗人SET8单克隆抗体,检测所有RCC组织及相应癌旁正常肾组织中SET8的表达情况,同时滴加β-catenin抗体检测其表达情况。比较SET8和β-catenin在RCC以及正常肾组织中表达水平的差异,分析其与患者临床信息、病理分期以及肿瘤细胞分级之间关系,SET8和β-catenin表达水平之间的关联性。结果 SET8在正常肾组织及RCC组织中的表达主要集中在细胞质中,细胞膜及细胞核亦有表达。β-catenin蛋白在正常肾组织中主要表达于肾小管上皮细胞的细胞膜。RCC中β-catenin出现细胞膜缺失或异位表达,SET8、β-catenin在RCC中的表达与肿瘤分级、病理分期密切相关(P<0.05)。SET8阳性表达率在RCC与癌旁正常肾组织中分别为76%(38/50)、66%(33/50),组间差异无统计学意义(P>0.05)。β-catenin蛋白异常表达在RCC及癌旁正常肾组织中分别为68%(34/50)、4%(2/50),组间差异有统计学意义(P<0.01)。SET8的阳性表达与β-catenin蛋白异常表达呈正相关(r=0.219,P<0.05)。结论 SET8激活的H4K20me-1调控着Wnt信号通路的激活与异常活动,影响基因转录与细胞活动,与RCC的发生、发展及远处转移存在密切联系。Objective The occurrence and progression of renal cell carcinoma（ RCC） is complicated process associated with DNA abnormal methylation,histone modification,and Wnt signaling pathway. This study aimed to investigate the expression of histone methylase SET8 in RCC,its relationship with the Wnt signaling pathway,its action mechanism in RCC,and its clinical significance.Methods We selected 50 cases of RCC treated by radical nephrectomy,detected the expression of SET8 in the RCC and adjacent noncancerous kidney tissues by immunohistochemical Eli Vision two-step staining with β-catenin. We compared the expression levels of SET8 and β-catenin in the two types of tissue and analyzed their relationship with the patients＇ clinical information and the pathologic stage and grade of tumor as well as the correlation between the SET8 and β-catenin expressions. Results SET8 was mainly express in the cytoplasm of the RCC and noncancerous kidney tissues,partially in the cell membrane and nucleus,while the β-catenin protein chiefly in the cell membrane of renal tubular epithelial cells in the normal kidney tissue. The expression levels of SET8 and β-catenin in the RCC tissue were closely related to the TNM stage and tumor grade（ P 〈0. 05）. The positive expression of SET8 in the RCC tissue（ 76% [38 /50]） showed no significant difference from that in the adjacent noncancerous kidney tissue（ 66% [33 /50]）（ P 〉0. 05）,but that of β-catenin was remarkably higher in the former（ 68%[34 /50]） than in the latter（ 4% [2 /50]）（ P〈 0. 01）. There was a positive correlation between the positive expression of SET8 and the abnormal expression of β-catenin（ r = 0. 219,P 〈0. 05）. Conclusion SET8-activated H4K20me-1 controls the activation and abnormal activities of the Wnt signaling pathway,affects the gene transcription and cell activity,and participates in the occurrence,progression,and distant metastasis of RCC.

关 键 词：肾细胞癌 SET8 Β-CATENIN 组蛋白甲基化 WNT信号通路 

分 类 号：R737.11[医药卫生—肿瘤]