【作者】 詹妍；

【导师】 周云峰；

【作者基本信息】 武汉大学 ， 临床医学， 2013， 博士

【摘要】 目的：探讨hTERT、UbE2D3及UbE2C在宫颈癌组织中的表达情况,分析三者基因编码蛋白在宫颈癌发生、发展过程中的作用和三者在宫颈癌中表达的相关性,以及hTERT、UbE2D3及UbE2C与宫颈癌临床病理因素之间的关系,研究三者对宫颈癌预后的影响,并探讨相关的分子病理学机制。材料与方法：回顾性分析2002年～2012年间武汉大学中南医院病理科保存的经手术切除宫颈癌蜡块组织标本173例,采用免疫组化法检测hTERT、UbE2D3及UbE2C在宫颈癌组织中的表达情况,hTERT、UbE2D3及UbE2C蛋白在不同分期不同级别宫颈癌组织中的表达阳性率的比较应用x~2检验和IFisher确切概率法,hTERT、UbE2D3及UbE2C对宫颈癌患者预后的影响采用Kaplan-Meier法及Log rank检验,hTERT、UbE2D3及UbE2C两者的表达相关性评价应用Kendall’s tau-b等级相关分析,影响宫颈癌患者的预后多因素分析采用Cox多因素分析法,P<0.05为差异有统计学意义。结果：hTERT蛋白阳性信号主要分布在细胞核中,而UbE2D3在细胞核及细胞浆中均有分布。宫颈癌组织中hTERT蛋自表达与患者年龄、病理类型、分期、分级无关,P>0.05,但与宫颈癌淋巴结转移密切相关,即有淋巴结转移组hTERT及阳性表达率显著高于无淋巴结转移组,P<0.05,同时UbE2D3蛋白表达与患者年龄、病理类型、分级无关,P>0.05,但与宫颈癌的分期及淋巴结转移相关,即分期晚者UbE2D3蛋白表达较分期早者低,同时,有淋巴结转移组UbE2D3阴性表达率显著高于无淋巴结转移组,P<0.05。UbE2C蛋白阳性信号在细胞核及细胞浆中均有分布。宫颈癌组织中UbE2C蛋白表达均与患者年龄、病理类型无关,P>0.05,但其表达与宫颈癌分期、分级、淋巴结转移密切相关,即分期高组UbE2C蛋白表达量显著高于分期较低组,分化程度高组UbE2C表达量显著低于分化程度低组,有淋巴结转移组UbE2C蛋白阳性表达率显著高于无淋巴结转移组,P<0.05。UbE2D3、UbE2C及hTERT的表达均与宫颈癌患者的预后相关,即UbE2D3表达量低的宫颈癌患者预后较表达量高者差,UbE2C及hTERT表达量高者较表达量低者预后差,差异具有统计学意义,P<0.05。宫颈癌组织中hTERT及UbE2D3蛋白表达呈负相关,有统计学意义(rk=-0.330,P<0.001),宫颈癌组织中hTERT及UbE2C蛋白表达呈正相关,有统计学意义(rk=0.483,P<0.001)。同时,Cox多因素法分析显示,hTERT蛋白表达水平,UbE2D3蛋白表达水平、UbE2C蛋白表达水平、肿瘤分级及淋巴结转移是影响宫颈癌预后的独立因素。结论：1、hTERT在细胞中的过度激活在宫颈癌的发生发展的过程中起着重要的作用。hTERT蛋白可以作为宫颈癌诊断和预后判断的分子标志物,是影响宫颈癌预后的独立因素,高hTERT表达提示宫颈癌患者预后不良。2、UbE2D3是宫颈癌发生发展过程中的保护性因素,与hTERT的表达呈负相关。UbE2D3是影响宫颈癌预后的独立因素,低UbE2D3表达提示宫颈癌患者预后不良。3、UbE2C与宫颈癌的发生发展,分期分级及预后密切相关,UbE2C不仅参与了宫颈癌变的起始阶段,同时也参与了癌变的全部进程,UbE2C与hTERT的表达正相关,UbE2C是影响宫颈癌患者预后的独立因素,高UbE2C表达提示宫颈癌患者预后不良。更多还原

【Abstract】 Objective Evaluate the expression of hTERT.UbE2D3, and UbE2C in cervical cancer tissue and analyze the role of these genes coding protein in the process of development and the correlation in cervical cancer, and the relationship between hTERT, UbE2D3,UbE2C and clinical pathological factors of cervical cancer, their effect on the prognosis of cervical cancer research, and explore the related mechanism of molecular pathology.Materials and Methods Clinical data of173cases of surgical tissue specimens from wax of patients with cervical cancer saved by the department of pathology of wuhan university zhongnan hospital between2002-2012were analyzed restrospectively. We use the immunohistochemical staining to detect the expression of hTERT, UbE2D3and UbE2C protein. We use SPSS17.0statistical software to do the statistical analysis, we use x2test and Fisher’s exact probability method to analyze different expression levels of hTERT, UbE2D3and UbE2C in different stages,classification,grade in cervical cancer tissue, hTERT, UbE2D3and UbE2C’s influence on the prognosis of patients with cervical cancer by Kaplan Meier-method and the Log rank test, the evaluation application of the correlation of the expression of hTERT and UbE2D3,UbE2C using Kendall’s tau-b rank correlation analysis, the factors affecting the prognosis of patients with cervical cancer using Cox multiple factors analysis, P<0.05for the difference was statistically significant.Results hTERT protein positive signals are mainly distributed in the nucleus, and UbE2D3are distributed both in the nucleus and cytoplasm. hTERT protein expression in cervical cancer tissue is not closely related to the patients age, pathological type, stage, grade, P>0.05, but is closely related to the cervical lymph node metastasis, which means positive expression rate of lymph node metastasis group hTERT was significantly higher than that of group without lymph node metastasis, P<0.05, at the same time UbE2D3protein expression has nothing to do with the patient age, pathology type, grade, P>0.05, but is associated with cervical cancer staging and lymph node metastasis,the later stage UbE2D3protein expression was lower than those of early stage early, at the same time, lymph node negative metastasis group UbE2D3expression rate was significantly higher than that of group lymph node metastasis, P<0.05). UbE2C protein positive signals were distributed in the nucleus and cytoplasm. UbE2C protein expression in cervical cancer tissue has nothing to do with patient’s age. pathology type. P>0.05, but its expression is closely related to the cervical cancer staging, grading and lymph node metastasis,which means the stage high group UbE2C protein expression are significantly higher than the low group, high degree of differentiation group UbE2C expression quantity is significantly lower than the low degree of differentiation, lymph node metastasis group UBE2C protein positive expression rate was significantly higher than that of group without lymph node metastasis, P<0.05). The expression of UbE2D3UbE2C and hTERT are associated with the prognosis of patients with cervical cancer.means that the lower the expression of UbE2D3is,the cervical cancer patients prognosis is the poorer, the higher the expression quantity of UbE2C and hTERT is,the poorer the prognosis is, the difference is statistically significant, P<0.05. The correlation between expression of hTERT and UbE2D3protein inCervical cancer tissue was statistically significant (fairly rk=0.330, P<0.001), and the expression relationship between UbE2C and hTERT protein in cervical cancer tissue were positively correlated,(fairly rk=0.483, P<0.001). At the same time, Cox multiple factor method analysis shows that protein expression levels of hTERT, UbE2D3,UbE2C, tumor grade and lymph node metastasis is the independent factors which affecting the prognosis of cervical cancer.Conclusions1,The excessive activation of hTERT in cells in the occurrence and development of cervical cancer plays an important role in the process. HTERT protein can be used as a cervical cancer diagnostic and prognostic molecular markers, were the independent factors influencing the prognosis of cervical cancer, high hTERT expression suggests poor prognosis of cervical cancer patients.2, UbE2D3is cervical cancer occur in the development of protective factors, and negatively correlated with the expression of hTERT. UbE2D3is the independent factors affecting the prognosis of cervical cancer, low UbE2D3expression suggests poor prognosis of cervical cancer patients.3, UbE2C development, with the incidence of cervical cancer staging classification and prognosis is closely related to UbE2C is not only involved in the initial stage of cervical cancer become, all at the same time also participated in the cancer process, UbE2C is positively related with the expression of hTERT, UbE2C is the independent factors affecting the prognosis of patients with cervical cancer, high UbE2C expression suggests poor prognosis of cervical cancer patients.更多还原