AGO1调节p53表达与肝细胞癌根治性切除患者预后的相关性  

The study of AGO1 regulates p53 expression and the prognosis of patients with hepatocellular carcinoma after curative resection

作　　者：王苗[1] 赵一鸣[1] 张绿[2] 汤钊猷[1] 樊嘉[1] 王鲁[1] 

机构地区：[1]复旦大学附属中山医院肝癌研究所肝肿瘤外科教育部癌变与侵袭原理重点实验室,上海200032 [2]复旦大学附属华山医院内分泌科

出　　处：《中华实验外科杂志》2014年第10期2094-2097,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81372314）

摘　　要：目的 探讨AGO1在肝细胞癌中的表达、功能及根治性切除术后的预后价值.方法 检测不同转移潜能的肝癌细胞株HCCLM3、MHCC97L和HepG2中AGO1 mRNA和蛋白表达.利用小干扰RNA,检测AGO1表达抑制后对HCCLM3和HepG2增殖侵袭功能和p53表达的影响.在200例行根治性切除的肝细胞癌患者肿瘤组织芯片中进行免疫组织化学染色,分析AGO1表达与患者预后的关系.结果 AGO1在人肝癌细胞株HCCLM3、MHCC97L及HepG2的mRNA表达量分别为0.400±0.025、0.188 ±0.022及0.154 ±0.019,高转移潜能肝癌细胞株表达显著高于低转移潜能肝癌细胞株（P＜0.05）.细胞增殖、侵袭及p53表达在AGO1表达抑制后显著下降.肿瘤组织中AGO1表达与较小的年龄（P＜0.05）、较高的血清甲胎蛋白（AFP）值（P＜0.01）、HBeAg阳性状态（P＜0.05）、肝硬化（P＜0.05）、肝内或肝外复发（P＜0.01）呈正相关,且为总体生存率（OS,P＜0.01）和无瘤生存率（DFS,P＜0.01）的独立危险因素.结论 AGO1可能提高了肝癌的增殖转移能力,且与p53通路相关.AGO1可能成为肝细胞癌的预后指标.Objective To investigate AGO1 expression,functions and prognostic value in Hepatocellular carcinoma patients underwent radical resection.Methods AGO1 expression was measured in HCCLM3,MHCC97L,and HepG2 cell lines.Using small interfering RNA,AGO1 functions and its effects on p53 were investigated in HCCLM3 and HepG2 cell lines.Immunohistochemistry in tissue microarrays consisting of 200 tumor tissue from hepatocellular carcinoma （HCC） patients underwent radical resection was used to analyze the AGO1 expression with prognosis.Results AGO1 mRNA expression in HCC cell lines HCCLM3,MHCC97L and HepG2 is 0.400 ± 0.025,0.188 ± 0.022 and 0.154 ± 0.019,increased in parallel with the metastatic potential of the HCC cell lines （P 〈 0.05）.Cell proliferation,invasion,and p53 expression significantly decreased after AGO1 depletion in the HCC cell lines.Intratumoral AGO1 was correlated with younger age （P 〈 0.05）,higher α-fetoprotein （P 〈 0.01）,HBeAg-positive status （P 〈0.05）,liver cirrhosis （P 〈 0.05）,intrahepatic and extrahepatic recurrence （P 〈 0.01）,and was an independent risk factor for overall survival （P 〈 0.01） and recurrence-free survival （P 〈 0.01）.Conclusion These findings indicate that AGO1 may promote HCC proliferation and metastasis through the P53 pathways,and AGO1 may be a reliable prognostic factor in HCC patients after resection.

关 键 词：AGO1 肝细胞癌 预后 P53 

分 类 号：R735.7[医药卫生—肿瘤]