【摘要】：目的:研究PCDH10在膀胱尿路上皮癌組織中的表達(dá)及其與患者臨床病理特征和預(yù)后的關(guān)系,為膀胱尿路上皮癌的診斷、惡性行為評(píng)估以及預(yù)后判斷提供理論依據(jù)和研究基礎(chǔ)。研究膀胱尿路上皮癌組織中PCDH10基因啟動(dòng)子甲基化狀態(tài),結(jié)合第一部分研究結(jié)果分析PCDH10基因啟動(dòng)子甲基化與其表達(dá)降低的相關(guān)性,并結(jié)合臨床病理資料分析PCDH10基因啟動(dòng)子甲基化與膀胱尿路上皮癌發(fā)生發(fā)展以及患者預(yù)后的關(guān)系,為膀胱尿路上皮癌的診斷、監(jiān)測(cè)以及預(yù)后判斷提供新的標(biāo)志物。研究PCDH10基因啟動(dòng)子甲基化在膀胱尿路上皮癌患者血清中的表達(dá),結(jié)合第二部分研究結(jié)果分析膀胱尿路上皮癌組織中PCDH10基因啟動(dòng)子甲基化與其在血清中表達(dá)的相關(guān)性,及其與患者臨床病理特征和預(yù)后的關(guān)系,為膀胱尿路上皮癌的診斷、惡性行為評(píng)估以及預(yù)后判斷提供理論依據(jù)和研究基礎(chǔ)。方法:應(yīng)用免疫組化的方法檢測(cè)PCDH10在33例正常膀胱粘膜組織和105例膀胱尿路上皮癌組織中的表達(dá),并與腫瘤的數(shù)目、大小、形態(tài)、分級(jí)、分期以及患者的年齡、性別和預(yù)后等臨床病理資料進(jìn)行統(tǒng)計(jì)學(xué)分析。應(yīng)用甲基化特異性PCR檢測(cè)105例膀胱尿路上皮癌組織和33例正常膀胱粘膜組織中PCDH10基因啟動(dòng)子甲基化狀態(tài),結(jié)合第一部分研究結(jié)果分析PCDH10基因啟動(dòng)子甲基化與其表達(dá)降低的相關(guān)性,并與腫瘤的數(shù)目、大小、形態(tài)、分級(jí)、分期以及患者的年齡、性別和預(yù)后等臨床病理資料進(jìn)行統(tǒng)計(jì)學(xué)分析。應(yīng)用甲基化特異性PCR檢測(cè)105例膀胱尿路上皮癌患者和33例正常對(duì)照組血清中PCDH10基因啟動(dòng)子甲基化狀態(tài),結(jié)合第二部分研究結(jié)果分析膀胱尿路上皮癌組織中PCDH10基因啟動(dòng)子甲基化與其血清表達(dá)減少的相關(guān)性,及其與患者臨床病理特征和預(yù)后的關(guān)系,并將結(jié)果進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果:(1)PCDH10在膀胱尿路上皮癌組織中表達(dá)降低,與其在正常膀胱粘膜中的表達(dá)相比有統(tǒng)計(jì)學(xué)意義;在膀胱尿路上皮癌組織中PCDH10表達(dá)降低與腫瘤生長(zhǎng)、復(fù)發(fā)、分化不良以及腫瘤浸潤(rùn)密切相關(guān),但與腫瘤數(shù)目、形態(tài)以及患者的年齡和性別無(wú)關(guān);此外,38例PCDH10表達(dá)正常的患者其5年總生存率為89.5%(34/38),67例PCDH10表達(dá)降低的患者其5年總生存率為64.2%(43/67),差異有統(tǒng)計(jì)學(xué)意義。(2)PCDH10基因在正常膀胱粘膜組織中未出現(xiàn)甲基化,在膀胱尿路上皮癌組織中其甲基化率為61.9%,差異有統(tǒng)計(jì)學(xué)意義;在膀胱尿路上皮癌組織中PCDH10基因啟動(dòng)子甲基化與其蛋白表達(dá)呈負(fù)相關(guān);PCDH10基因啟動(dòng)子甲基化與腫瘤生長(zhǎng)、分化不良、浸潤(rùn)以及患者的不良預(yù)后密切相關(guān),但與腫瘤數(shù)目、形態(tài)以及患者的年齡和性別無(wú)關(guān)。(3)PCDH10基因在正常對(duì)照組血清中未出現(xiàn)甲基化,在膀胱尿路上皮癌患者血清中其甲基化率為55.2%,差異有統(tǒng)計(jì)學(xué)意義;在膀胱尿路上皮癌組織中PCDH10基因啟動(dòng)子甲基化與其在血清中基因啟動(dòng)子甲基化呈正相關(guān);膀胱尿路上皮癌患者血清中PCDH10基因啟動(dòng)子甲基化與腫瘤生長(zhǎng)、分化不良、浸潤(rùn)以及患者的不良預(yù)后密切相關(guān),但與腫瘤數(shù)目、形態(tài)以及患者的年齡和性別無(wú)關(guān)。結(jié)論:膀胱尿路上皮癌組織中PCDH10表達(dá)降低并且與腫瘤的生長(zhǎng)、分化不良、浸潤(rùn)以及患者的不良預(yù)后密切相關(guān),這些結(jié)果表明PCDH10表達(dá)降低是膀胱尿路上皮癌發(fā)生發(fā)展和患者預(yù)后不良的一個(gè)危險(xiǎn)因素。PCDH10基因啟動(dòng)子甲基化與其蛋白表達(dá)呈負(fù)相關(guān),啟動(dòng)子甲基化是導(dǎo)致PCDH10表達(dá)降低的主要原因;并且PCDH10基因啟動(dòng)子甲基化與腫瘤的生長(zhǎng)、分化不良、浸潤(rùn)以及患者的不良預(yù)后密切相關(guān),這些結(jié)果表明膀胱尿路上皮癌組織中PCDH10基因啟動(dòng)子甲基化是膀胱尿路上皮癌發(fā)生發(fā)展和患者預(yù)后不良的一個(gè)標(biāo)志物。PCDH10基因啟動(dòng)子甲基化在血清中與在膀胱尿路上皮癌組織中PCDH10基因啟動(dòng)子甲基化呈正相關(guān);而且血清中PCDH10基因啟動(dòng)子甲基化與腫瘤生長(zhǎng)、分化不良、浸潤(rùn)以及患者的不良預(yù)后密切相關(guān),這些結(jié)果表明膀胱尿路上皮癌患者血清中PCDH10基因啟動(dòng)子甲基化是膀胱尿路上皮癌發(fā)生發(fā)展和患者預(yù)后不良的一個(gè)標(biāo)志物。
[Abstract]:Objective: To study the expression of PCDH10 in bladder urothelial carcinoma and its relationship with clinicopathological features and prognosis, and to provide theoretical basis and research basis for the diagnosis, malignant behavior evaluation and prognosis of bladder urothelial carcinoma. Part of the results analyzed the correlation between the methylation of the promoter of PCDH10 gene and its decreased expression, and the relationship between the methylation of the promoter of PCDH10 gene and the occurrence, development and prognosis of bladder urothelial carcinoma. To investigate the expression of methylation of PCDH10 gene promoter in serum of patients with bladder urothelial carcinoma and to analyze the correlation between methylation of PCDH10 gene promoter and its expression in serum of patients with bladder urothelial carcinoma. Methods: The expression of PCDH10 in 33 normal bladder mucosa tissues and 105 bladder urothelial carcinoma tissues was detected by immunohistochemistry. The expression of PCDH10 was correlated with the number, size, shape, classification, stage, age, sex and prognosis of the tumor. The methylation status of PCDH10 gene promoter in 105 bladder urothelial carcinoma tissues and 33 normal bladder mucosa tissues was detected by methylation-specific PCR. The correlation between the methylation status of PCDH10 gene promoter and the decrease of its expression was analyzed with the results of the first part of the study. Methylation-specific PCR was used to detect the methylation status of PCDH10 gene promoter in 105 patients with bladder urothelial carcinoma and 33 normal controls. The results of the second part of the study were combined to analyze the P Results: (1) The expression of PCDH10 in bladder urothelial carcinoma was significantly lower than that in normal bladder mucosa, and the expression of PCDH10 in bladder urothelial carcinoma was significantly lower than that in normal bladder mucosa. In addition, the 5-year overall survival rate of 38 patients with normal expression of PCDH10 was 89.5% (34/38), and that of 67 patients with decreased expression of PCDH10 was 64.2% (43/67). The difference was statistically significant. (2) There was no methylation of PCDH10 gene in normal bladder mucosa, and the methylation rate in bladder urothelial carcinoma was 61.9%. The methylation of PCDH10 gene promoter was negatively correlated with its protein expression in bladder urothelial carcinoma. There was no methylation of PCDH10 gene in the serum of normal control group, and the methylation rate was 55.2% in the serum of patients with bladder urothelial carcinoma. The methylation of the promoter of PCDH10 gene was positively correlated with the methylation of the promoter in serum in epithelial carcinoma; the methylation of the promoter of PCDH10 gene in serum of patients with bladder urothelial carcinoma was closely related to tumor growth, poor differentiation, infiltration and poor prognosis, but was related to the number, morphology, age and sex of patients with bladder urothelial carcinoma. Conclusion: The decreased expression of PCDH10 in bladder urothelial carcinoma is closely related to tumor growth, poor differentiation, infiltration and poor prognosis. These results suggest that the decreased expression of PCDH10 is a risk factor for the occurrence, development and poor prognosis of bladder urothelial carcinoma. The expression of PCDH10 protein was negatively correlated with promoter methylation, which was the main reason for the decrease of PCDH10 expression, and the promoter methylation of PCDH10 gene was closely related to the growth, poor differentiation, invasion and poor prognosis of bladder urothelial carcinoma. The methylation of the promoter of PCDH10 gene in serum is positively correlated with the methylation of the promoter of PCDH10 gene in bladder urothelial carcinoma tissues, and the methylation of the promoter of PCDH10 gene in serum is closely related to tumor growth, poor differentiation, invasion and poor prognosis of patients. These results suggest that methylation of the promoter of PCDH10 gene in serum of patients with bladder urothelial carcinoma is a marker of the occurrence, development and poor prognosis of bladder urothelial carcinoma.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.14

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