DNMT1联合HMGA2在膀胱尿路上皮癌中的表达及其意义

发布时间：2019-01-10 08:24

【摘要】：背景：膀胱癌(bladder cancer, BC)在目前男性泌尿生殖系统肿瘤位居前列,根据最新流行病学调查研究显示BC的发病率位于全球恶性疾病第六位”,在美国BC每年新发现病例超过5000例,在国内,男性膀胱癌的发病率排到了第八位,女性则排到了第十位,其中90%以上均为膀胱尿路上皮癌(Bladder Urothelial carcinoma, BUC)是BC发病的主要病理类型,但BUC的诊断与治疗方法并未有历史性的突破,因此诊治等方面的研究是至关重要的。目的：本研究通过检测DNA甲基转移酶(DNMT1)及高迁移率蛋白A2(HMGA2)在膀胱尿路上皮癌中的表达变化情况,探索HMGA2及DNMT1在膀胱尿路上皮癌临床病理分期、预后及诊疗价值等方面的意义。方法：收集从2012年1月至2014年2月在河南省人民医院泌尿外科收集的48例膀胱尿路上皮癌标本设为实验组,同期20例正常的膀胱组织设为对照组,利用蛋白免疫印迹(Western Blotting, WB)、(免疫组化,SP)以及反转录聚合酶链式反应(RT-PCR)三种方法检测两组标本的DNMT1和HMGA2的蛋白／基因水平变化情况。结果： (1).蛋白免疫印迹(Western Blotting, WB)结果显示：DNMT1和HMGA2蛋白在实验组标本中的表达量高于对照组正常膀胱组织中的表达量,其显著差异有统计学意义(P0.05)； (2).免疫组化(SP)结果显示：DNMT1和HMGA2蛋白在膀胱尿路上皮癌组织中的阳性表达率分别为68.5%和62.9%,显著高于正常膀胱组织中的表达25.0%(x2=6.872,P=0.010)和20.0%,其差异有统计学意义(x2=8.637,P=0.002)； (3). DNMT1和HMGA2在病理分级级别高、浸润性及伴有转移的膀胱尿路上皮癌标本中的阳性表达率明显高于病理分级级别低、浅表性、无肿瘤转移的膀胱尿路上皮癌标本的阳性表达率,二者差异有统计学意义(P0.05)； (4).RT-PCR结果显示：DNMT1和HMGA2在实验组标本中的表达水平明显高于对照组(x2=6.264, P=0.001),且差异具有统计学意义(P0.05)； (5).DNMT1和HMGA2蛋白的表达水平变化与患者年龄、性别、肿瘤的大小无正相关关系(P0.05)； (6).DNMT1在膀胱尿路上皮癌组织中的表达水平和HMGA2在膀胱尿路上皮癌组织中的表达水平呈正相关(r=0.627,P=0.04)；结论： (1).膀胱尿路上皮癌组织中DNMT1和HMGA2水平明显高于正常膀胱组织； (2). DNMT1和HMGA2的表达水平变化与肿瘤的病理分级、浸润性及转移性密切相关； (3).DNMT1和HMGA2可能会作为判断膀胱尿路上皮癌发生发展的潜在诊断指标； (4). DNMT1在膀胱尿路上皮癌组织中的表达和HMGA2在膀胱尿路上皮癌组织中的表达呈正相关关系,二者可能成为联合检测膀胱尿路上皮癌的诊断指标之一：
[Abstract]:Background: bladder cancer (bladder cancer, BC) is currently in the forefront of male urogenital tumors. According to the latest epidemiological studies, the incidence of BC is the sixth most common malignant disease in the world. More than 5000 new cases are found in BC every year in the United States. In China, the incidence of bladder cancer in men ranks eighth, and in women it ranks tenth, more than 90% of which are bladder epithelial carcinoma (Bladder Urothelial carcinoma,. BUC) is the main pathological type of BC, but there is no historical breakthrough in the diagnosis and treatment of BUC, so it is very important to study the diagnosis and treatment of BUC. Objective: to investigate the expression of DNA methyltransferase (DNMT1) and high mobility protein A2 (HMGA2) in bladder urothelial carcinoma and to explore the clinicopathologic stages of HMGA2 and DNMT1 in bladder urothelial carcinoma. Significance of prognosis and value of diagnosis and treatment. Methods: from January 2012 to February 2014, 48 specimens of bladder urothelial carcinoma were collected from urology department of Henan Provincial people's Hospital as experimental group and 20 normal bladder tissues as control group. Western blot (Western Blotting, WB), (immunohistochemical, SP) and reverse transcriptase chain reaction (RT-PCR) were used to detect the changes of protein / gene levels of DNMT1 and HMGA2 in the two groups. Results: (1). Western blot (Western Blotting, WB) results showed that the expression of DNMT1 and HMGA2 protein in the experimental group was higher than that in the normal bladder tissue of the control group, and the difference was statistically significant (P0.05); (2). The positive expression rates of DNMT1 and HMGA2 protein in bladder urothelial carcinoma were 68.5% and 62.9%, respectively, which were significantly higher than those in normal bladder tissue (25.0%). The difference was statistically significant between 0.010 and 20.0 (x2o8.637). (3) The positive expression rate of DNMT1 and HMGA2 in bladder urothelial carcinoma with invasion and metastasis was significantly higher than that in bladder urothelial carcinoma with low grade, superficial grade and no tumor metastasis. The difference was statistically significant (P0.05). (4) RT-PCR results showed that the expression of DNMT1 and HMGA2 in the experimental group was significantly higher than that in the control group (x2ch6.264, P0. 001), and the difference was statistically significant (P0.05). (5) there was no positive correlation between the expression of DNMT1 and HMGA2 protein and age, sex and tumor size (P0.05). (6) there was a positive correlation between the expression of DNMT1 in bladder urothelial carcinoma and the expression of HMGA2 in bladder urothelial carcinoma (r 0. 627) .Conclusion: (1) there was a positive correlation between the expression of DNMT1 in bladder urothelial carcinoma and the expression of HMGA2 in bladder urothelial carcinoma. The levels of DNMT1 and HMGA2 in bladder urothelial carcinoma were significantly higher than those in normal bladder. (2). The expression of DNMT1 and HMGA2 were closely related to the pathological grade, invasion and metastasis of the tumor. (3) DNMT1 and HMGA2 might be used as potential diagnostic indicators to judge the occurrence and development of bladder urothelial carcinoma. (4). There was a positive correlation between the expression of DNMT1 in bladder urothelial carcinoma and the expression of HMGA2 in bladder urothelial carcinoma, which might be one of the diagnostic indexes for combined detection of bladder urothelial carcinoma.
【学位授予单位】：新乡医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.14

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