柯萨奇病毒和腺病毒受体CAR与结直肠癌临床病理相关性及介导腺病毒基因治疗的潜在作用研究

发布时间：2018-05-30 13:11

本文选题：CAR + 结直肠癌　；参考：《浙江大学》2016年硕士论文

【摘要】：目的：研究柯萨奇病毒和腺病毒受体CAR在结直肠癌中的表达并分析其与结直肠癌临床病理的相关性,探讨诱导结直肠癌细胞CAR表达上调的药物及在腺病毒介导的基因治疗的潜在作用。资料和方法：采用免疫组化对251例结直肠癌组织及对应的251例癌旁正常组织行免疫组化染色,根据染色的强度及面积分析结直肠癌组织中CAR的表达。探讨CAR表达与结直肠癌临床病理特性的相关性。生存分析CAR表达与结直肠患者预后的相互关系。比较毒理基因组数据库(CTD)分析可以诱导CAR表达增高的药物,分析可能用于提高基因腺病毒治疗疗效的策略。结果：免疫组化结果显示CAR主要表达于结直肠癌细胞的胞膜及胞浆中,正常结直肠组织中CAR阳性表达率为95.6%.(240/251),显著高于结直肠癌组织的40.6%(102/251)(p0.001,)；分析其表达与结直肠癌临床病理特性的关系发现,CAR表达在结直肠癌肝转移中的阳性率为83.3%(5/6),显著高于无结直肠癌肝转移组(39.6%,97/245,p=0.042)；CAR表达与结直肠癌其他临床病理特征无显著相关性。进一步分析了CAR在结直肠癌细胞膜上的表达,结果发现结直肠正常组织中CAR的表达为29.5%(74/251),显著高于结直肠癌患者中CAR的表达(4.0%,10/251, p0.001). Kaplan-Meier生存分析显示CAR的表达与结直肠患者术后生存率无显著相关性。Cox回归模型进一步分析发现结直肠癌远处转移是结直肠癌患者预后的独立风险因子(p=0.001),CAR的表达与预后无单独相关性(p=0.335)。比较基因组数据库(CTD)分析发现一些药物如PJ-34、骨化三醇等能上调CAR的表达。结论：CAR在结直肠癌组织中表达下调,高表达的CAR可能促进结直肠癌的肝转移；通过腺病毒结构改造或者药物诱导CAR达增高可以提高腺病毒介导的基因转染效率。
[Abstract]:Objective: to study the expression of coxsackie virus (Coxsackie) and adenovirus receptor (CAR) in colorectal cancer and to analyze the correlation between coxsackie virus and adenovirus receptor CAR in colorectal cancer. To investigate the potential role of drugs in inducing up-regulation of CAR expression in colorectal cancer cells and in adenovirus-mediated gene therapy. Materials and methods: immunohistochemical staining was performed in 251 cases of colorectal carcinoma and 251 cases of adjacent normal tissues. The expression of CAR was analyzed according to the intensity and area of the staining. To investigate the correlation between CAR expression and clinicopathological characteristics of colorectal cancer. Survival analysis: correlation between CAR expression and prognosis of colorectal patients. CTD-based Toxicology Genomic Database (CTD-based) analysis can induce increased CAR expression of drugs, analysis may be used to improve the efficacy of gene adenovirus treatment strategies. Results: immunohistochemical results showed that CAR was mainly expressed in the cell membrane and cytoplasm of colorectal cancer cells. The positive rate of CAR expression in normal colorectal tissues was 95.6 / 250 / 251, which was significantly higher than that in colorectal cancer tissues (40.610 / 251P 0.001). The relationship between the expression and clinicopathological characteristics of colorectal cancer showed that the positive rate of car expression in liver metastasis of colorectal cancer was 83.33 / 5 / 6, which was significantly higher than that in colorectal cancer. There was no significant correlation between the expression of car and other clinicopathological features of colorectal cancer. The expression of CAR on the cell membrane of colorectal cancer was further analyzed. The results showed that the expression of CAR in normal colorectal tissues was 29.5kum / 251g, which was significantly higher than that in colorectal cancer patients (4.0% / 251, p0.001). Kaplan-Meier survival analysis showed that there was no significant correlation between the expression of CAR and postoperative survival rate in colorectal cancer patients. Cox regression model showed that distant metastasis of colorectal cancer was an independent risk factor for the prognosis of colorectal cancer patients. There was no separate correlation between the two groups. Comparative genomic database (CTD) analysis showed that some drugs such as PJ-34 and ossifying triol could upregulate the expression of CAR. Conclusion the expression of CAR in colorectal carcinoma is down-regulated, and the high expression of CAR may promote the liver metastasis of colorectal cancer, and adenovirus-mediated gene transfection efficiency can be improved by adenovirus structural modification or drug induced increase of CAR.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.34

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