结合胆汁酸通过晚期糖基化终产物受体（RAGE）促进胆管癌生长及侵袭作用的分子机制研究

发布时间：2018-11-08 06:46

【摘要】：第一部分RAGE在胆管癌中的表达及其临床意义背景及目的:胆管癌(Cholangiocarcinoma,CCA)是一种诊断率低且死亡率极高的恶性肿瘤。晚期糖基化终产物受体(The receptor for advanced glycation end products,RAGE)是一种跨膜受体,属于免疫球蛋白超家族中的一员,RAGE的表达可参与到多种肿瘤的发展过程,但其具体机制尚未完全明确。本研究意在研究RAGE在胆管癌中的表达及促进胆管癌发生的分子机制。方法:回顾性分析于我院收集的51例胆管癌标本及相关临床资料,免疫组化检测RAGE在胆管癌患者组织中的表达,研究RAGE的表达与胆管癌患者肿瘤大小、INM分期等之间的关系。结果:RAGE评分≥4的患者为41人(约占80.4%),RAG≥8的患者为24人(约占47.1%)。RAGE的表达与肿瘤的分化程度密切相关,且RAGE≥8为影响胆管癌生存时间的显著的危险因素(HR 2.199;95%CI 1.072-4.511;p=0.032),亚组分析中发现:RAGE≥8与胆管癌患者的生存时间(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)密切相关。结论:RAGE的表达与胆管癌患者的预后密切相关。第二部分结合胆汁酸可通过RAGE促进胆管癌的增殖、侵袭及转移背景及目的:胆管癌是主要起源于胆管上皮细胞的恶性肿瘤,约占原发性肝癌的10-25%。但其发生及发展机制尚不明确。已有文献报道胆汁酸的异常代谢可增加胆管癌的发生率,胆管癌早期症状不明显,常因胆汁淤积引起的临床表现被人们发觉。因此,本研究拟在研究胆汁酸在胆管癌发展过程中的作用。方法:收集胆管癌及胆管结石患者ERCP术后胆汁酸各20例,采用高效液相色谱法分析胆汁中结合胆汁酸(TCA)、游离胆汁酸(DCA)的含量。qRT-PCR、western blotting、CCK8、Transwell等方法检测胆汁酸与RAGE在胆管癌发展过程中的相互作用。结果:TCA可促进胆管癌细胞的增殖、侵袭及转移;敲除RAGE后,可显著抑制TCA引起的促进胆管癌进展的作用;TCA可通过RAGE,进而激活p-ERK信号通路,从而促进胆管癌的进展。结论:TCA可通过RAGE,从而促进胆管癌的进展。
[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，

本文编号：2317689