PCDH10在膀胱尿路上皮癌中的表达及其启动子甲基化的临床研究

发布时间：2018-09-12 18:25

【摘要】：目的:研究PCDH10在膀胱尿路上皮癌组织中的表达及其与患者临床病理特征和预后的关系,为膀胱尿路上皮癌的诊断、恶性行为评估以及预后判断提供理论依据和研究基础。研究膀胱尿路上皮癌组织中PCDH10基因启动子甲基化状态,结合第一部分研究结果分析PCDH10基因启动子甲基化与其表达降低的相关性,并结合临床病理资料分析PCDH10基因启动子甲基化与膀胱尿路上皮癌发生发展以及患者预后的关系,为膀胱尿路上皮癌的诊断、监测以及预后判断提供新的标志物。研究PCDH10基因启动子甲基化在膀胱尿路上皮癌患者血清中的表达,结合第二部分研究结果分析膀胱尿路上皮癌组织中PCDH10基因启动子甲基化与其在血清中表达的相关性,及其与患者临床病理特征和预后的关系,为膀胱尿路上皮癌的诊断、恶性行为评估以及预后判断提供理论依据和研究基础。方法:应用免疫组化的方法检测PCDH10在33例正常膀胱粘膜组织和105例膀胱尿路上皮癌组织中的表达,并与肿瘤的数目、大小、形态、分级、分期以及患者的年龄、性别和预后等临床病理资料进行统计学分析。应用甲基化特异性PCR检测105例膀胱尿路上皮癌组织和33例正常膀胱粘膜组织中PCDH10基因启动子甲基化状态,结合第一部分研究结果分析PCDH10基因启动子甲基化与其表达降低的相关性,并与肿瘤的数目、大小、形态、分级、分期以及患者的年龄、性别和预后等临床病理资料进行统计学分析。应用甲基化特异性PCR检测105例膀胱尿路上皮癌患者和33例正常对照组血清中PCDH10基因启动子甲基化状态,结合第二部分研究结果分析膀胱尿路上皮癌组织中PCDH10基因启动子甲基化与其血清表达减少的相关性,及其与患者临床病理特征和预后的关系,并将结果进行统计学分析。结果:(1)PCDH10在膀胱尿路上皮癌组织中表达降低,与其在正常膀胱粘膜中的表达相比有统计学意义;在膀胱尿路上皮癌组织中PCDH10表达降低与肿瘤生长、复发、分化不良以及肿瘤浸润密切相关,但与肿瘤数目、形态以及患者的年龄和性别无关;此外,38例PCDH10表达正常的患者其5年总生存率为89.5%(34/38),67例PCDH10表达降低的患者其5年总生存率为64.2%(43/67),差异有统计学意义。(2)PCDH10基因在正常膀胱粘膜组织中未出现甲基化,在膀胱尿路上皮癌组织中其甲基化率为61.9%,差异有统计学意义;在膀胱尿路上皮癌组织中PCDH10基因启动子甲基化与其蛋白表达呈负相关;PCDH10基因启动子甲基化与肿瘤生长、分化不良、浸润以及患者的不良预后密切相关,但与肿瘤数目、形态以及患者的年龄和性别无关。(3)PCDH10基因在正常对照组血清中未出现甲基化,在膀胱尿路上皮癌患者血清中其甲基化率为55.2%,差异有统计学意义;在膀胱尿路上皮癌组织中PCDH10基因启动子甲基化与其在血清中基因启动子甲基化呈正相关;膀胱尿路上皮癌患者血清中PCDH10基因启动子甲基化与肿瘤生长、分化不良、浸润以及患者的不良预后密切相关,但与肿瘤数目、形态以及患者的年龄和性别无关。结论:膀胱尿路上皮癌组织中PCDH10表达降低并且与肿瘤的生长、分化不良、浸润以及患者的不良预后密切相关,这些结果表明PCDH10表达降低是膀胱尿路上皮癌发生发展和患者预后不良的一个危险因素。PCDH10基因启动子甲基化与其蛋白表达呈负相关,启动子甲基化是导致PCDH10表达降低的主要原因;并且PCDH10基因启动子甲基化与肿瘤的生长、分化不良、浸润以及患者的不良预后密切相关,这些结果表明膀胱尿路上皮癌组织中PCDH10基因启动子甲基化是膀胱尿路上皮癌发生发展和患者预后不良的一个标志物。PCDH10基因启动子甲基化在血清中与在膀胱尿路上皮癌组织中PCDH10基因启动子甲基化呈正相关;而且血清中PCDH10基因启动子甲基化与肿瘤生长、分化不良、浸润以及患者的不良预后密切相关,这些结果表明膀胱尿路上皮癌患者血清中PCDH10基因启动子甲基化是膀胱尿路上皮癌发生发展和患者预后不良的一个标志物。
[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.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R737.14

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