文章摘要
李云龙,王 梅,付鲁渝,刘淑岩,王桂兰,陈 莉.肝癌中TLR3信号分子与自噬相关基因表达的相关性及临床意义[J].南京医科大学学报,2016,(11):1285~1294
肝癌中TLR3信号分子与自噬相关基因表达的相关性及临床意义
Correlation and clinical significance of TLR3 signaling molecules and autophagy related gene expression in hepatocellular carcinoma
投稿时间:2016-07-01  
DOI:10.7655/NYDXBNS20161102
中文关键词: 肝细胞肝癌  凋亡  自噬  临床病理因素  预后  LC3  Beclin1  TLR3  TRIF
英文关键词: hepatocellular carcinoma  apoptosis  autophagy  clinicopathologic factors  prognosis  LC3  Beclin1  TLR3  TRIF
基金项目:
作者单位
李云龙 南通大学医学院病理学系,江苏 南通 226001 
王 梅 南通大学医学院病理学系,江苏 南通 226001 
付鲁渝 南通大学医学院病理学系,江苏 南通 226001 
刘淑岩 南通大学医学院病理学系,江苏 南通 226001 
王桂兰 南通大学医学院病理学系,江苏 南通 226001 
陈 莉 南通大学医学院病理学系,江苏 南通 226001 
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中文摘要:
      目的:研究肝细胞肝癌(hepatocellular carcinoma,HCC)中Toll样受体3(Toll-like receptor 3,TLR3)及信号分子含TIR结构域的转接蛋白(TIR-domain-containing adaptor protein including IFN-β,TRIF)表达与细胞自噬相关蛋白Beclin1和LC3表达的相关性及临床意义,并探讨相关机制?方法:收集与随访101例HCC病例,构建肝组织芯片?HE染色判断HCC的组织分化,免疫组化染色检测HCC组织中Ki-67?TLR3?TRIF? LC3 和Beclin l的表达,应用TUNEL方法检测肿瘤细胞凋亡信号?统计学分析其临床病理因素和预后?结果:本组HCC中TLR3和TRIF表达呈正相关(ρ=0.640,P < 0.001),其高表达分别与肿瘤HbsAg感染?硬化背景?细胞凋亡指数(apoptosis index,AI)及患者5年总生存率呈正相关,与肿瘤细胞增殖?血管浸润?Edmondson分级和TNM分期呈负相关?Beclin1和LC3表达呈显著正相关(ρ=0.587,P < 0.001),两者高表达分别与肿瘤脉管浸润?Edmondson分级?TNM分期?肿瘤细胞增殖呈正相关,与AI和预后呈负相关?并且TLR3?TRIF分别与LC3 和Beclin1的表达呈负相关(P均<0.001)?结论:HCC中TLR3及其信号分子TRIF表达,细胞自噬相关基因Beclin1和LC3的表达分别通过调控细胞增殖?凋亡和自噬来影响肿瘤的生物学行为和预后?HCC组织中Beclin1介导的自噬途径与TLR3信号凋亡通路存在交叉,两条通路异常可能是HCC发生?进展的机制之一?
英文摘要:
      Objective:This paper focus on the correlation and clinical pathological significance of toll-like receptor 3(TLR3) and its signal molecules TIR-domain-containing adaptor protein including IFN-β (TRIF) and autophagy related gene,LC3 and Beclin 1,expressions in human hepatocellular carcinoma (HCC),and its relevant mechanism. Methods:We collected and followed-up 101 cases of HCC cases,and built tissue microarray. HE staining for HCC tissue differentiation and immunohistochemical staining were performed to detect the expression of Ki-67 (cell proliferation marker),TLR3,TRIF,LC3 and Beclin 1,respectively. TUNEL was performed to detect the apoptotic signals of cancer cells. Statistical analysis was performed to analyze its correlation with cancer clinical pathological factors and prognosis. Results:In HCC,the expressions of TLR3 and TRIF were positive correlated(ρ=0.640,P < 0.001). Its high expression was positively correlated with HbsAg infection,cirrhosis background,cell apoptosis index(AI) and total 5-year survival rate,and negatively correlated with cancer cell proliferation,vascular invasion,Edmondson grading and TNM staging. Beclin1 and LC3 expression was significantly positive correlated(ρ=0.587,P < 0.001). Both high expressions were respectively positively correlated with vascular infiltration,Edmondson grading,TNM staging and cancer cell proliferation,but negatively correlated with apoptosis index(AI) and 5-year survival rate(P < 0.001). TLR3 and TRIF respectively negatively correlated with the expression of LC3 and Beclin 1(both P < 0.001). Conclusion:The expressions of TLR3 and signaling molecules TRIF,cell autophagy related gene Beclin1 and LC3 respectively influence the biological behavior and prognosis of HCC by regulating cell proliferation,apoptosis and autophagy. There are cross points existing between Beclin1 mediated autophagy pathway and TLR3 mediated apoptosis pathway in HCC. Abnormalities of the two pathways may be one of the mechanisms in HCC occurrence and progress.
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