肝细胞癌组织microRNA-187-3p表达预后意义

目的 微小RNA (microRNA,miRNA)差异表达与多种肿瘤的发生发展密切相关,但微小RNA-187-3p(miR-187-3p)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达及预后意义研究较少.本研究检测HCC组织中microRNA的表达谱,分析miR-187-3p在HCC组织中的表达及其与临床病理特征之间的关系,探讨miR-187-3p表达在其发生、发展及预后中的作用.方法 利用microRNA芯片杂交技术筛选5例HCC组织及相应癌旁组织中差异表达的microRNA,然后通过实时荧光定量PCR(real-time fuorescence quantitative-PCR,RFQ-PCR)法验证86例HCC组织及相应癌旁组织中miR-187-3p表达水平,并统计临床病理资料,随访生存期.结果 148个microRNAs在HCC组织中差异表达,其中102个microRNAs在HCC组织较相应癌旁组织表达下调,46个microRNAs在HCC组织较相应癌旁组织表达上调.RFQ-PCR结果显示,miR-187-3p在HCC组织中表达水平明显低于相应癌旁组织,差异有统计学意义,Z=-2.244,P=0.025.HCC中miR-187-3p表达状态与肿瘤大小(x2=5.031,P=0.025)相关,而与性别(x2=3.648,P=0.056)、年龄(x2=0.003,P=0.956)、是否转移(x2=0.005,P=0.943)、TNM分期(x2=0.129,P=0.719)、肿瘤数目(x2 =0.126,P=0.722)、乙肝表面抗原(x2=0.019,P=0.890)、AFP水平(x2=0.187,P=0.665)和Child分级(x2=1.665,P=0.197)无关.miR-187-3p低表达的HCC患者总生存期较高表达者明显缩短,x2=7.684,P=0.006.且多因素分析发现,miR-187-3p表达水平和TNM分期是影响HCC患者生存预后的独立危险因素.结论 miR-187-3p在一定程度上参与了HCC的发生发展,其有望成为HCC新的潜在的治疗靶点以及诊断、判断病情和预测预后的分子标志物.

Expression and prognostic significance of miR-187-3p in hepatocellular carcinoma

OBJECTIVE Abnormal expression of microRNA plays important roles in the development and progression of many cancers.However,the role of miR-187-3p in the express and prognosis of hepatocellular carcinoma is still unkown.The study aimed to test the expression profile of microRNA in hepatocellular carcinoma tissues,and analyze the expression of microRNA-187-3p(miR-187-3p) in hepatocellular carcinoma and its relationship with clinicopathologic features,and to discuss the role of expression of miR-187-3p in its development and prognosis.METHODS The microRNA chip hybridization technology was adopted to screen 5 patients of microRNAs with different expression both in hepatocellular carcinoma tissues and adjacent tissues,and then verifying the expression level of miR-187-3p in 86 patients of hepatocellular carcinoma tissues and adjacent tissues by real-time fuorescence quantitative-PCR(RFQ-PCR),and calculating clinicopathologic parameters and following up the survival of hepatocellular carcinoma patients.RESULTS Totally 148 of microRNAs with different expression in hepatocellular carcinoma were found,of them 102 microRNAs in hepatocellular carcinoma tissues were down-regulated expression than that in adjacent tissues and 46 microRNAs were completely opposite.The results of RFQ-PCR proved that the expression level of miR-187-3p in hepatocellular carcinoma tissues was obviously lower than that in adjacent tissues.The difference was statistically significant (Z=-2.244,P=0.025).The expression status of miR-187-3p in hepatocellular carcinoma was relevant to tumor size (x2 =5.031,P=0.025),but not to gender(x2 =3.648,P=0.056),age(x2 =0.003,P=0.956),metastasis or not (x2 =0.005,P=0.943),TNM stage (x2 =0.129,P=0.719),tumor number (x2 =0.126,P=0.722),HBsAg (x2 =0.019,P=0.890),AFP level (x2 =0.187,P=0.665) and Child-Pugh classification (x2=1.665,P=0.197).The survival time of hepatocellular carcinoma patients with lower expression of miR-187-3p was shorter than that with higher expression of miR-187-3p (x2 =7.684,P =0.006).Multivariate analysis showed that the expression level of miR-187-3p and TNM stage were independently prognostic significant.CONCLUSION miR-187-3p may be partly involved in the occurrence and development of hepatocellular carcinoma,it may be expected to become a potential therapeutic target for hepatocellular carcinoma and a molecular marker for diagnosis,evaluation of illness and prognosis.