CAJ | 학술논문

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.
목적 신세포암( renal cell carcinoma , RCC)적발생발전시다인소작용하적복잡과정, DNA이상갑기화、조단백수식화Wnt신호통로등영향착RCC적발생발전. 문중지재연구조단백갑기화매( histone methylase SET domain containing 8, SET8)재RCC조직중적표체,탐토기여Wnt 신호통로적관련급재RCC중적작용궤제급림상의의. 방법 채용단순수궤추양법선취2010년지2012년엄서장족자치구인민의원적RCC표본50례,운용HE염색화면역조화염색(이급계분법)급통과적가토항인SET8 단극륭항체,검측소유RCC조직급상응암방정상신조직중SET8적표체정황,동시적가β-catenin항체검측기표체정황. 비교SET8화β-catenin재RCC이급정상신조직중표체수평적차이,분석기여환자림상신식、병리분기이급종류세포분급지간관계,SET8 화β-catenin 표체수평지간적관련성. 결과 SET8재정상신조직급RCC조직중적표체주요집중재세포질중,세포막급세포핵역유표체. β-catenin 단백재정상신조직중주요표체우신소관상피세포적세포막. RCC 중β-catenin출현세포막결실혹이위표체,SET8、β-catenin재RCC중적표체여종류분급、병리분기밀절상관(P<0.05). SET8양성표체솔재RCC 여암방정상신조직중분별위76%(38/50)、66%(33/50),조간차이무통계학의의(P>0.05). β-catenin 단백이상표체재RCC급암방정상신조직중분별위68%(34/50)、4%(2/50),조간차이유통계학의의(P<0.01). SET8적양성표체여β-catenin 단백이상표체정정상관(r=0.219,P<0.05). 결론 SET8격활적H4K20me-1조공착Wnt신호통로적격활여이상활동,영향기인전록여세포활동,여RCC적발생、발전급원처전이존재밀절련계.
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 SET 8 in the RCC and adjacent noncancerous kidney tissues by immunohistochemical EliVision 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 SET 8 andβ-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 theβ-catenin protein chiefly in the cell membrane of renal tubular epithelial cells in the normal kidney tissue .The expression levels of SET 8 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 ad-jacent 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 SET 8 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 .