【摘要】：第一部分RAGE在膽管癌中的表達(dá)及其臨床意義背景及目的:膽管癌(Cholangiocarcinoma,CCA)是一種診斷率低且死亡率極高的惡性腫瘤。晚期糖基化終產(chǎn)物受體(The receptor for advanced glycation end products,RAGE)是一種跨膜受體,屬于免疫球蛋白超家族中的一員,RAGE的表達(dá)可參與到多種腫瘤的發(fā)展過程,但其具體機(jī)制尚未完全明確。本研究意在研究RAGE在膽管癌中的表達(dá)及促進(jìn)膽管癌發(fā)生的分子機(jī)制。方法:回顧性分析于我院收集的51例膽管癌標(biāo)本及相關(guān)臨床資料,免疫組化檢測RAGE在膽管癌患者組織中的表達(dá),研究RAGE的表達(dá)與膽管癌患者腫瘤大小、INM分期等之間的關(guān)系。結(jié)果:RAGE評分≥4的患者為41人(約占80.4%),RAG≥8的患者為24人(約占47.1%)。RAGE的表達(dá)與腫瘤的分化程度密切相關(guān),且RAGE≥8為影響膽管癌生存時間的顯著的危險因素(HR 2.199;95%CI 1.072-4.511;p=0.032),亞組分析中發(fā)現(xiàn):RAGE≥8與膽管癌患者的生存時間(HR 5.716;95%CI 1.456-22.448;p=0.012)及 TNM 分期(HR 1.040;95%CI 1.003-1.079;p=0.036)密切相關(guān)。結(jié)論:RAGE的表達(dá)與膽管癌患者的預(yù)后密切相關(guān)。第二部分結(jié)合膽汁酸可通過RAGE促進(jìn)膽管癌的增殖、侵襲及轉(zhuǎn)移背景及目的:膽管癌是主要起源于膽管上皮細(xì)胞的惡性腫瘤,約占原發(fā)性肝癌的10-25%。但其發(fā)生及發(fā)展機(jī)制尚不明確。已有文獻(xiàn)報道膽汁酸的異常代謝可增加膽管癌的發(fā)生率,膽管癌早期癥狀不明顯,常因膽汁淤積引起的臨床表現(xiàn)被人們發(fā)覺。因此,本研究擬在研究膽汁酸在膽管癌發(fā)展過程中的作用。方法:收集膽管癌及膽管結(jié)石患者ERCP術(shù)后膽汁酸各20例,采用高效液相色譜法分析膽汁中結(jié)合膽汁酸(TCA)、游離膽汁酸(DCA)的含量。qRT-PCR、western blotting、CCK8、Transwell等方法檢測膽汁酸與RAGE在膽管癌發(fā)展過程中的相互作用。結(jié)果:TCA可促進(jìn)膽管癌細(xì)胞的增殖、侵襲及轉(zhuǎn)移;敲除RAGE后,可顯著抑制TCA引起的促進(jìn)膽管癌進(jìn)展的作用;TCA可通過RAGE,進(jìn)而激活p-ERK信號通路,從而促進(jìn)膽管癌的進(jìn)展。結(jié)論:TCA可通過RAGE,從而促進(jìn)膽管癌的進(jìn)展。
[Abstract]:Part I expression of RAGE in cholangiocarcinoma and its clinical significance background and objective: cholangiocarcinoma (Cholangiocarcinoma,CCA) is a malignant tumor with low diagnostic rate and high mortality. Advanced glycation end product receptor (The receptor for advanced glycation end products,RAGE) is a transmembrane receptor, which belongs to the immunoglobulin superfamily. The expression of RAGE may participate in the development of many kinds of tumors, but its specific mechanism has not been completely clarified. The purpose of this study was to investigate the expression of RAGE in cholangiocarcinoma and its molecular mechanism. Methods: the clinical data of 51 cases of cholangiocarcinoma collected in our hospital were analyzed retrospectively. The expression of RAGE in cholangiocarcinoma tissues was detected by immunohistochemistry, and the relationship between the expression of RAGE and tumor size and INM stage of cholangiocarcinoma was studied. Results: there were 41 patients (80.4%) with RAGE score 鈮，

本文編號：2317689