MicroRNA-34a、Notch1在肝细胞肝癌组织中的表达及临床意义  

Clinical significance of expression of microRNA-34a and Notch1 in hepatocellular carcinoma

作　　者：于泳[1] 李霄[1] 周亮[1] 窦科峰[1] 李小磊[1] 阮柏[1] 张卓超[1] 戴斌[1] 汪建林[1] 杨西胜 王德盛[1] 

机构地区：[1]中国人民解放军第四军医大学西京医院肝胆胰脾外科,陕西省西安市710032

出　　处：《世界华人消化杂志》2014年第14期1943-1952,共10页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.30872480;陕西省社会发展攻关基金资助项目;No.2012SF2-09-1;中国人民解放军第四军医大学西京医院助推计划基金资助项目;No.XJZT11Y15~~

摘　　要：目的:观察microRNA-34a、Notch1在肝细胞肝癌(hepatocellular carcinoma,HCC)组织的表达,探讨其与HCC发生、发展、临床病理特征的关系及可能的临床意义.方法:在132例HCC组织及癌旁组织、49例正常肝脏组织中应用实时荧光定量PCR法检测microRNA-34a的表达和免疫组织化学染色检测Notch 1表达.结果:HCC组织中microRNA-34a表达水平明显低于癌旁组织(2.57±0.71,P=0.003)及正常肝组织(8.65±0.21,P<0.001),在转移性癌组织中microRNA-34a表达水平明显低于非转移性癌组织(1.34±0.13,P=0.014),差异均有统计学意义.Notch1的免疫组织化学染色结果:HCC组织中Notch1表达水平明显高于癌旁组织(3.12±0.67,P=0.001)及正常肝组织(4.65±0.14,P<0.001),转移性癌组织高于非转移性癌组织(2.14±0.37,P=0.008),差异有统计学意义.MicroRNA-34a与Notch1在HCC及癌旁组织中均成负相关,相关系数分别为(r=-0.259,P=0.003)、(r=-0.274,P=0.002),两者在HCC组织中的表达与患者年龄、性别、肝功能、肿瘤部位、是否合并肝硬变、是否伴随肝炎病毒感染及甲胎蛋白(α-fetoprotein,αFP或AFP)含量无相关性(P>0.05),而与肿瘤恶性程度、肿瘤个数、肿瘤体积、淋巴结转移、浸润深度、TNM分期密切相关(P<0.05).Kaplan-Meier分析显示:microRNA-34a低表达、Notch1高表达组患者术后3年生存率(11.3%),明显低于microRNA-34a高表达、Notch1低表达组(34.7%),差异具有统计学意义(χ2=38.163,P=0.011).结论:MicroRNA-34a在HCC组织中较癌旁和正常肝脏组织明显减低,其通过逆向调节靶蛋白Notch1参与肿瘤肿瘤恶性行为;检测microRNA-34a及Notch1在HCC组织中的表达情况,对HCC的临床诊断、治疗及预后判断有潜在的重要意义.AIM： To detect the expressions of microRNA-34a and Notch1 in hepatocellular carcinoma（HCC）and to explore their relationships with HCC occurrence and development and the clinical and pathological features of HCC. METHODS： Real-time RT-PCR and immunohistochemistry were used to detect the expression of microRNA-34a and Notch1 protein in 132 HCC tissues, matched tumor-adjacent tissues and 49 normal liver tissues, respectively. RESULTS： The expression of microRNA-34a in HCC tissues were significantly lower than that in tumor-adjacent tissues（P = 0.003） and normal liver tissues（P〈 0.001）. The expression of microRNA-34a in HCC tissues with metastasis was significantly lower than that in HCC tissues without metastasis（P = 0.014）. The expression of Notch1 was significantly higher in HCC tissues than in tumor-adjacent tissues（P = 0.001） and normal liver tissues（P 〈0.001）. The expression of Notch1 in HCC tissues with metastasis was significantly lower than that in HCC tissues without metastasis（P = 0.008）. The expression of microRNA-34a was negatively correlated with that of Notch1 in HCC and tumor-adjacent tissues（r =-0.259, P = 0.003; r =-0.274, P = 0.002）. The expression of microRNA-34a and Notch1 in HCC had no correlation with patient age, gender, liver cirrhosis, tumor site, viral hepatitis, or AFP（P 0.05 for all）, but was closely correlated with tumor malignancy, tumor size, lymph node metastasis, tumor number, infiltration depth, and TNM stage（P 0.05 for all）. The 3-year survival rate in the group with low expression of microRNA-34a and high expression of Notch1（11.3%） was significantly lower than that in the group with high expression of microRNA-34a and low expression of Notch1（34.7%）（χ2 = 38.163, P = 0.011）. CONCLUSION： The expression of microRNA-34a is significantly down-regulated in HCC tissues, which may reversely regulate its target protein Notch1. Detecting the expression of microRNA-34a and Notch1 in HCC had a potentialsignificance for diagnosi

关 键 词：肝脏肿瘤 肝细胞肝癌 癌旁组织 MicroRNA-34a NOTCH1 生存分析 免疫组织化学 

分 类 号：R735.7[医药卫生—肿瘤]