肾细胞癌组织中的组蛋白甲基化酶表达及其临床意义

发布时间：2019-03-03 00:19

【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(P0.05)。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(P0.05)。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(P0.01)。SET8的阳性表达与β-catenin蛋白异常表达呈正相关(r=0.219,P0.05)。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。
[Abstract]:Objective the carcinogenesis and development of renal cell carcinoma (renal cell carcinoma,RCC) is a complex process under the action of multiple factors. Abnormal methylation of DNA, histone modification and Wnt signaling pathway affect the occurrence and development of RCC. The purpose of this study was to investigate the expression of protein methylase (histone methylase SET domain containing-8 (set-8) in RCC and to explore its association with Wnt signaling pathway and its mechanism and clinical significance in RCC. Methods from 2010 to 2012, 50 RCC samples from Guangxi Zhuang Autonomous region people's Hospital from 2010 to 2012 were selected by simple random sampling. HE staining, immunohistochemical staining (second grade score) and dropping rabbit anti-human SET8 monoclonal antibody were used. The expression of SET8 was detected in all RCC tissues and normal renal tissues adjacent to cancer, and the expression of SET8 was detected by dropping 尾-catenin antibody. The expression levels of SET8 and 尾-catenin in RCC and normal renal tissues were compared. The relationship between the expression level of SET8 and 尾-catenin and the clinical information, pathological stage and tumor cell grade of the patients were analyzed. The correlation between the expression level of SET8 and 尾-catenin was also analyzed. Results the expression of SET8 was mainly concentrated in cytoplasm in normal renal tissue and RCC tissue. 尾-catenin protein was mainly expressed in the cell membrane of renal tubular epithelial cells, 尾-catenin was absent or ectopic expressed in RCC, and the expression of SET8, 尾-catenin in RCC was related to tumor grade. The positive expression rate of et-8 was 76% (38 / 50) in RCC and 66% (33 / 50) in paracancerous normal renal tissue, respectively. There was no significant difference between groups (P0.05). The abnormal expression of 尾-catenin protein was 68% (34 / 50) in RCC and 4% (2 / 50) in paracancerous normal renal tissue, respectively. There was a significant difference between the two groups (P0.01). There was a positive correlation between the positive expression of ET8 and the abnormal expression of 尾-catenin protein (r = 0.219, P0.05). Conclusion H4K20me-1 activated by SET8 regulates the activation and abnormal activity of Wnt signaling pathway, affects gene transcription and cellular activity, and is closely related to the occurrence, development and distant metastasis of RCC.
【作者单位】：广西壮族自治区人民医院泌尿外科;南京军区南京总医院泌尿外科;
【基金】：国家自然基金项目(81372742)
【分类号】：R737.11

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