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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Hbs Ag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。
Objective: To investigate the expression of Toll-like receptor 3 (TLR3) and TIR-domain containing adapter protein (IFN-β) in hepatocellular carcinoma (HCC) , TRIF) expression and the expression of autophagy-related proteins Beclin1 and LC3 and its clinical significance, and to explore the relevant mechanisms. Methods: 101 HCC cases were collected and followed up to construct the liver tissue chip. Tissue differentiation of HCC was determined by HE staining. The expression of Ki-67, TLR3, TRIF, LC3 and Beclin 1 in HCC tissues was detected by immunohistochemistry. TUNEL method was used to detect the signal of tumor cells apoptosis. Statistical analysis of its clinicopathological factors and prognosis. Results: There was a positive correlation between TLR3 and TRIF expression in HCC (ρ = 0.640, P <0.001). The high expression of TLR3 and TRIF in HCC tissues correlated with tumor Hbs Ag infection, sclerotic background, apoptosis index (AI) Survival rate was positively correlated with tumor cell proliferation, vascular invasion, Edmondson grade and TNM stage was negatively correlated. The expression of Beclin1 and LC3 was positively correlated (P = 0.587, P <0.001). The high expression of Beclin1 and LC3 was positively correlated with tumor vessel invasion, Edmondson classification, TNM stage and tumor cell proliferation respectively, but negatively correlated with AI and prognosis. TLR3 and TRIF were negatively correlated with the expression of LC3 and Beclin1 (all P <0.001). CONCLUSION: The expression of TLR3 and its signaling molecule TRIF in HCC and the expression of autophagy-related genes Beclin1 and LC3 affect the biological behavior and prognosis of tumor respectively by regulating cell proliferation, apoptosis and autophagy. Beclin1-mediated autophagy pathway crosses with TLR3 signaling pathway in HCC. The abnormality of both pathways may be one of the mechanisms of HCC development.