發(fā)布時(shí)間：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統(tǒng)腫瘤位居前列,根據(jù)最新流行病學(xué)調(diào)查研究顯示BC的發(fā)病率位于全球惡性疾病第六位”,在美國(guó)BC每年新發(fā)現(xiàn)病例超過5000例,在國(guó)內(nèi),男性膀胱癌的發(fā)病率排到了第八位,女性則排到了第十位,其中90%以上均為膀胱尿路上皮癌(Bladder Urothelial carcinoma, BUC)是BC發(fā)病的主要病理類型,但BUC的診斷與治療方法并未有歷史性的突破,因此診治等方面的研究是至關(guān)重要的。 目的： 本研究通過檢測(cè)DNA甲基轉(zhuǎn)移酶(DNMT1)及高遷移率蛋白A2(HMGA2)在膀胱尿路上皮癌中的表達(dá)變化情況,探索HMGA2及DNMT1在膀胱尿路上皮癌臨床病理分期、預(yù)后及診療價(jià)值等方面的意義。 方法： 收集從2012年1月至2014年2月在河南省人民醫(yī)院泌尿外科收集的48例膀胱尿路上皮癌標(biāo)本設(shè)為實(shí)驗(yàn)組,同期20例正常的膀胱組織設(shè)為對(duì)照組,利用蛋白免疫印跡(Western Blotting, WB)、(免疫組化,SP)以及反轉(zhuǎn)錄聚合酶鏈?zhǔn)椒磻?yīng)(RT-PCR)三種方法檢測(cè)兩組標(biāo)本的DNMT1和HMGA2的蛋白／基因水平變化情況。 結(jié)果： (1).蛋白免疫印跡(Western Blotting, WB)結(jié)果顯示：DNMT1和HMGA2蛋白在實(shí)驗(yàn)組標(biāo)本中的表達(dá)量高于對(duì)照組正常膀胱組織中的表達(dá)量,其顯著差異有統(tǒng)計(jì)學(xué)意義(P0.05)； (2).免疫組化(SP)結(jié)果顯示：DNMT1和HMGA2蛋白在膀胱尿路上皮癌組織中的陽性表達(dá)率分別為68.5%和62.9%,顯著高于正常膀胱組織中的表達(dá)25.0%(x2=6.872,P=0.010)和20.0%,其差異有統(tǒng)計(jì)學(xué)意義(x2=8.637,P=0.002)； (3). DNMT1和HMGA2在病理分級(jí)級(jí)別高、浸潤(rùn)性及伴有轉(zhuǎn)移的膀胱尿路上皮癌標(biāo)本中的陽性表達(dá)率明顯高于病理分級(jí)級(jí)別低、淺表性、無腫瘤轉(zhuǎn)移的膀胱尿路上皮癌標(biāo)本的陽性表達(dá)率,二者差異有統(tǒng)計(jì)學(xué)意義(P0.05)； (4).RT-PCR結(jié)果顯示：DNMT1和HMGA2在實(shí)驗(yàn)組標(biāo)本中的表達(dá)水平明顯高于對(duì)照組(x2=6.264, P=0.001),且差異具有統(tǒng)計(jì)學(xué)意義(P0.05)； (5).DNMT1和HMGA2蛋白的表達(dá)水平變化與患者年齡、性別、腫瘤的大小無正相關(guān)關(guān)系(P0.05)； (6).DNMT1在膀胱尿路上皮癌組織中的表達(dá)水平和HMGA2在膀胱尿路上皮癌組織中的表達(dá)水平呈正相關(guān)(r=0.627,P=0.04)； 結(jié)論： (1).膀胱尿路上皮癌組織中DNMT1和HMGA2水平明顯高于正常膀胱組織； (2). DNMT1和HMGA2的表達(dá)水平變化與腫瘤的病理分級(jí)、浸潤(rùn)性及轉(zhuǎn)移性密切相關(guān)； (3).DNMT1和HMGA2可能會(huì)作為判斷膀胱尿路上皮癌發(fā)生發(fā)展的潛在診斷指標(biāo)； (4). DNMT1在膀胱尿路上皮癌組織中的表達(dá)和HMGA2在膀胱尿路上皮癌組織中的表達(dá)呈正相關(guān)關(guān)系,二者可能成為聯(lián)合檢測(cè)膀胱尿路上皮癌的診斷指標(biāo)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.
【學(xué)位授予單位】：新鄉(xiāng)醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.14

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