Caveolin1论文Caveolin1在喉鳞癌中表达情况与HPV病毒感染关系的研究

Caveolin1论文Caveolin1在喉鳞癌中表达情况与HPV病毒感染关系的研究 Caveolin-1论文:Caveolin-1在喉鳞癌中表达情况与HPV病毒感染关系的研究 【中文摘要】膜窖蛋白Caveolae是细胞膜内陷形成的直径为50-100nm烧瓶状的特殊膜结构,其中小窖蛋白-1(Caveolin-1)为膜窖蛋白Caveolae的标志性膜蛋白,般认为它与细胞内外特异性物质的运输相关。Caveolin-1在某些恶性肿瘤中缺失或低表达,故可能为肿瘤抑癌基因;但是它在少数肿瘤(如前列腺癌,结肠癌等)中是高表达且表现为能促进肿瘤细胞的增殖和转移,以上结果表明Caveolin-1在不同类型的肿瘤细胞中可能具有的不同作用。人类乳头瘤病毒(Human Papilloma Virus, HPV)是喉粘膜感染的常见病毒,被认为与喉鳞癌的发生密切相关,其中最常见和高危的类型为HPV16/18亚型。HPV是一种亲上皮的DNA病毒,感染易感细胞-上皮基底细胞后具有促上皮增长、促瘤形成的特性。病毒感染易感细胞的内吞途径有多种,其中Caveolin-1介导的内吞可能是HPV进入宿主细胞的主要方式。现有关Caveolin-1的研究逐渐成为肿瘤研究领域新的热点,但喉鳞癌组织中Caveolin-1表达情况及与16/18型HPV病毒感染之间的关系尚不清楚。本实验分别采用免疫组织化学和原位杂交技术对Caveolin-1在喉鳞癌中的表达情况和HPV16/18病毒感染情况进行检测和分析,以探讨喉鳞癌中Caveolin-1的表达情况及其与HPV病毒感染的关系,为喉鳞癌的早期预防和生物治疗提供理论依据。研究喉鳞状细胞癌中Caveolin-1的表达情况及与人类乳头瘤病毒(HPV)感染 之间的关系,探讨两者对喉鳞癌生物学行为的影响。方法:收集山东大学齐鲁医院耳鼻喉头颈外科2008年1月-6月期间手术的66例喉鳞癌标本,其中42例有相对应的癌旁组织(距离肿瘤边缘?0.5cm),所取标本均经病理学检查明确诊断。患者术前均未接受放,化疗、生物治疗,其中男61例,女5例,年龄49,74岁,中位年龄59.2岁。肿瘤发生部位:声门上型21例,声门型22例,声门下型23例。根据国际抗癌联盟(2003年版)TNM分期改进法进行临床分期:?期9例,?期12例,?期27例,?期18例;颈部淋巴结转移情况:无颈淋巴结转移17例,有颈淋巴结转移49例。病理组织学分级:角化型39例,未角化型27例。标本离体后立即放入4%多聚甲醛固定,常规石蜡包埋,连续切片厚度4 u m。分别应用免疫组织化学和原位杂交方法检测喉鳞癌中Caveolin-1蛋白及HPV病毒感染的情况,统计学分析两者之间的相关性,探讨两者与喉鳞癌生物学行为的关系。结果:Caveolin-1蛋白在喉鳞癌和癌旁组织中的表达率分别为71.2%和9.52%,两者表达有显著差异(p<0.05); Caveolin-1蛋白的表达程度与病理类型、TNM分期、颈部淋巴结转移显著相关。喉鳞癌中HPV感染阳性率为55.1%,癌旁组织中为21.4%,两者表达差异有统计学意义(p<0.05);HPV感染与患者年龄、病理类型、TNM分期和转移均无关。在本实验中喉鳞癌Caveolin-1表达与HPV感染之间呈正相关表达(r=0.62,x2=10.40,p<0.05)。结论:喉鳞癌中Caveolin-1表达明显增高并与恶性生物学行为有关,Caveolin-1检测可以作为判断喉鳞癌生物学的指标之一;HPV感染是喉鳞癌发生的高危因素,并且 Caveolin-1与HPV两者之间存在协同作用。 【英文摘要】Background:Among these was 50 to100nm inaginations of the plasma membrane referred to as either caveolae intracellulare, due to their cave-like appearance, or plasmalemmal vesicles. The molecular nature of caveolae could be explored following the identification of its signature protein, caveolin. Caveolae being implicated and demonstrated to be important in a variety of cellular functions including endocytic processes,cholesterol and lipid homeostasis, signal transduction,and tumor suppression. Although caveolae and the caveolins are continuously implicated in an increasing array of cellular processes, it is clear that their physiological roles are vastly different depending on the cell type and organ system examined. In this regard, insights into caveolar function will not only be interesting from the stand point of cell biology but will be rewarding in understanding mammalian physiology with applications to human disease. Human Papilloma Virus (HPV) infection is the major etiological factor of Laryngeal squamous cell carcinomas (LSCC). Most of the LSCC patients complicated with HPV 16 and/or 18 type infection. HPV can promote the proliferation and oncogenesis of the basal epithelial cell, but the mechanisms are not clear. One of the mechanisms is that HPV can lead into the basal epithelial cell by Caveolae, so that they lead to the formation of LSCC. The pathogenesis of HPV has been one of the important aspects of the study for etiology of laryngeal carcinoma virus. This paper analyzed the relationship of the Caveolin-1 to the occurrence of laryngeal carcinoma and the relationship of laryngeal carcinoma to the HPV16/18 infection and the relationship between the HPV 16/18 infection and expression of Caveolin-1 to the location, differentiation, metastasis and recurrence of laryngeal carcinoma. It is the purpose of this paper to provide a link between the expression of caveolae in LSCC and the level of HPV and to provide useful information for the predication and treatment of laryngeal carcinoma as early as possible.:To investigate the expression of Caveolin-1 and its correlation with the infection of HPV in human LSCC and to analyse their influences on the biological behavior of human LSCC. This study aim to provided a basic theory and evidence to gene therapy for human LSCC.Methods:Formalin-fixed and paraffin embedded LSCC cases from 66 Laryngeal neoplasms patients and 42 cases with Para-cancerous tissues were tested for Caveolin-1 and HPV 16/18 type expressions by immunocytochemical staining or in-situ hybridization respectively. Results were analyzed with the clinical pathologic parameters and survival.Results:The positive rates of Caveolin-1 in human LSCC and Para-cancerous tissues were respectively 71.2% and 9.52%(p0.05). The expressions of Caveolin-1 and infection of HPV in LSCC had a positive correlation(r=0.62,χ2 = 10.40, p<0.05).Conclusion:Expression of Caveolin-1 was significantly higher in human LSCC than in Para-cancerous tissues. Caveolin-1 had significant relations to tumor invasion and lymph node metastasis. The pathogenesis of laryngeal squamous cell carcinoma was closely related with the HPV 16/18 infection. And the mechanism might be that Caveoiln-1 mediated the infection of HPV in human LSCC. 【关键词】Caveolin-1 喉恶性肿瘤 鳞状细胞癌 人乳头瘤病毒 【英文关键词】Caveolin-1 Laryngeal neoplasms Squamous of carcinoma Human papilloma virus 【目录】Caveolin-1在喉鳞癌中表达情况与HPV病毒感染关系 的研究 中文摘要 6-8 ABSTRACT 8-9 符号说明 11-12 前言 12-13 与方法 13-18 结果 18-19 讨论 19-26 结论 26-27 参考文献 27-30 综述 30-44 参考文献 39-44 本文附图表 44-49 致谢 49-50 攻读硕士学位期间发表的学术论文 50-51 学位论文评阅及答辩情况表 51