【作者】 杜晓琴；

【导师】 郝权；

【作者基本信息】 天津医科大学 ， 肿瘤学， 2008， 硕士

【摘要】 目的分析研究高迁移率族蛋白1(HMGB1)和晚期糖基化终产物受体(RAGE)基因在宫颈鳞癌、癌旁、正常宫颈组织中的表达,探讨它们与宫颈鳞癌发生、侵袭和转移的相关性。并进一步研究HMGB1在宫颈癌细胞中的表达,为进一步探讨HMGB1参与宫颈肿瘤生物学行为的具体机制奠定基础。方法组织:宫颈鳞癌根治术后冻存癌及癌旁组织各60例,正常宫颈组织30例。通过SYBR Green I嵌合荧光实时定量PCR技术检测HMGB1及RAGE基因在宫颈鳞癌、癌旁、正常宫颈组织及宫颈鳞癌临床参数指标中的定性,定量表达。细胞:选择人宫颈癌细胞及人成纤维细胞,应用SYBR Green I嵌合荧光实时定量PCR及细胞免疫组化技术进一步检测HMGB1基因及蛋白的表达。结果1.HMGB1 mRNA在宫颈鳞癌、癌旁组织表达水平明显高于在正常宫颈组织的表达,HMGB1mRNA在宫颈鳞癌、癌旁组织的表达水平无明显的统计学差异。RAGE mRNA在宫颈鳞癌、癌旁及正常宫颈组织中的表达水平均无明显的统计学差异。2.宫颈鳞癌组织中HMGB1mRNA的表达与肿瘤分期、淋巴转移相关,与肿瘤直径、分级无关。RAGE mRNA在宫颈鳞癌组织中的表达与肿瘤直径、分级和分期均无关,仅与淋巴转移相关。在宫颈鳞癌组织中,HMGB1 mRNA及RAGE mRNA表达水平行相关分析,淋巴转移组中显示二者表达水平存在显著相关性(r=0.883,P＜0.05)。3.从细胞水平研究HMGB1在人宫颈癌细胞及正常人成纤维细胞中的表达情况,发现HMGB1基因及蛋白在人宫颈癌细胞中的表达水平明显高于正常人成纤维细胞。结论1.HMGB1 mRNA可能与宫颈鳞癌发生、发展、侵袭、转移密切相关,从基因水平确定HMGB1为宫颈癌相关癌基因。2.RAGE mRNA可能增强了宫颈鳞癌淋巴转移能力。RAGE mRNA的表达与HMGB1 mRNA的表达在宫颈癌淋巴转移组中的正相关性分析结果,提示可能在宫颈鳞癌的转移过程中,RAGE mRNA与HMGB1mRNA起协同作用,增强了下游基因的信号传导,起到促进转移的作用。HMGB1/RAGE轴可能是促进宫颈癌转移发生的重要信号通路。3.从细胞水平上检测HMGB1基因、蛋白在人宫颈癌细胞中的高表达,提示HMGB1与人宫颈癌细胞恶性生物学行为的相关性。更多还原

【Abstract】 ObjectiveTo investigate expression and clinico-pathological findings of high mobility group box1(HMGB1)mRNA and receptor for advanced glycation end products (RAGE)mRNA in cervical squamous carcinoma,to explore their roles during carcinoma process,invasion and metastasis,to study the expression of HMGB1 in cell of cervical cancer,At both of gene and protein level determined HMGB1 as a novel oncogene correlative with cervical cancer.MethodsTissue:60 cervical squamous carcinoma samples,60 paraneoplastic samples and 30 normal cervical samples.Upon collection,the samples were frozen immediately at -80℃for future analysis.Real time Quantitative polymerase chain reaction was employed to detect the expression of HMGB1 mRNA and RAGE mRNA in cervical squamous carcinoma and nomal cervical tissues.Cell:choose cervical carcinoma cell and fibroblast cell.Real time Quantitative polymerase chain reaction and immunohistochemistry were employed to detect the expression of HMGB1.Results1.The expression of HMGB1 mRNA in cervical squamous carcinoma and their paraneoplastic tissues was higher than that in normal cervix tissues.And expression of RAGE was no significantly differences between cervical squamous carcinoma,paraneoplastic and normal cervical tissues.2.The overexpression of HMGB1 mRNA in the cancer tissues was significantly correlated with the stage,the presence of metastasis,but not correlated with the diameter and grade of tumor.Statistical analysis showed that RAGE mRNA has a relation with the metastasis.But no relation in stage,diameter and grade of tumor.3.At both of gene and protein level determined HMGB1 as a novel oncogene correlative with cervical cancer cell.Conclusion1.HMGB1 could be a prognostic predictor of growth、invasion、malignant degree in the evaluation of cervical cancer.HMGB1 is the main mechanism correlated with the metastasis of cervical cancer and they may become new targets for treating lyphatic metastasis.2.RAGE expression was not significantly different among these tissue types,and showed no significant correlation with the different clinical parameters.However there was a significant positive correlation betwwen the expression of HMGB1 and RAGE in the cervical cancer metastasis group.3.The expression of HMGB1 mRNA in the cervical cancer cell was higher than that in normal cell.and the The expression of HMGB1 protein in the cervical cancer cell was positive.This will help us to find out the relationship between HMGB1 and biological behaviour of cervical cancer.更多还原