本文選題：CAR + 結(jié)直腸癌��； 參考：《浙江大學(xué)》2016年碩士論文

【摘要】：目的：研究柯薩奇病毒和腺病毒受體CAR在結(jié)直腸癌中的表達(dá)并分析其與結(jié)直腸癌臨床病理的相關(guān)性,探討誘導(dǎo)結(jié)直腸癌細(xì)胞CAR表達(dá)上調(diào)的藥物及在腺病毒介導(dǎo)的基因治療的潛在作用。資料和方法：采用免疫組化對(duì)251例結(jié)直腸癌組織及對(duì)應(yīng)的251例癌旁正常組織行免疫組化染色,根據(jù)染色的強(qiáng)度及面積分析結(jié)直腸癌組織中CAR的表達(dá)。探討CAR表達(dá)與結(jié)直腸癌臨床病理特性的相關(guān)性。生存分析CAR表達(dá)與結(jié)直腸患者預(yù)后的相互關(guān)系。比較毒理基因組數(shù)據(jù)庫(kù)(CTD)分析可以誘導(dǎo)CAR表達(dá)增高的藥物,分析可能用于提高基因腺病毒治療療效的策略。結(jié)果：免疫組化結(jié)果顯示CAR主要表達(dá)于結(jié)直腸癌細(xì)胞的胞膜及胞漿中,正常結(jié)直腸組織中CAR陽(yáng)性表達(dá)率為95.6%.(240/251),顯著高于結(jié)直腸癌組織的40.6%(102/251)(p0.001,)；分析其表達(dá)與結(jié)直腸癌臨床病理特性的關(guān)系發(fā)現(xiàn),CAR表達(dá)在結(jié)直腸癌肝轉(zhuǎn)移中的陽(yáng)性率為83.3%(5/6),顯著高于無(wú)結(jié)直腸癌肝轉(zhuǎn)移組(39.6%,97/245,p=0.042)；CAR表達(dá)與結(jié)直腸癌其他臨床病理特征無(wú)顯著相關(guān)性。進(jìn)一步分析了CAR在結(jié)直腸癌細(xì)胞膜上的表達(dá),結(jié)果發(fā)現(xiàn)結(jié)直腸正常組織中CAR的表達(dá)為29.5%(74/251),顯著高于結(jié)直腸癌患者中CAR的表達(dá)(4.0%,10/251, p0.001). Kaplan-Meier生存分析顯示CAR的表達(dá)與結(jié)直腸患者術(shù)后生存率無(wú)顯著相關(guān)性。Cox回歸模型進(jìn)一步分析發(fā)現(xiàn)結(jié)直腸癌遠(yuǎn)處轉(zhuǎn)移是結(jié)直腸癌患者預(yù)后的獨(dú)立風(fēng)險(xiǎn)因子(p=0.001),CAR的表達(dá)與預(yù)后無(wú)單獨(dú)相關(guān)性(p=0.335)。比較基因組數(shù)據(jù)庫(kù)(CTD)分析發(fā)現(xiàn)一些藥物如PJ-34、骨化三醇等能上調(diào)CAR的表達(dá)。結(jié)論：CAR在結(jié)直腸癌組織中表達(dá)下調(diào),高表達(dá)的CAR可能促進(jìn)結(jié)直腸癌的肝轉(zhuǎn)移；通過(guò)腺病毒結(jié)構(gòu)改造或者藥物誘導(dǎo)CAR達(dá)增高可以提高腺病毒介導(dǎo)的基因轉(zhuǎn)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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.34

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本文編號(hào)：1955419