肝癌患者血清中4种miRNAs的表达研究

Four Kinds of miRNAs in Hepatocellular Carcinoma Patients Serum Expression Research

目的探讨肝细胞肝癌(hepatocellular carcinoma,HCC)简称肝癌患者血清中miR-21、miR-221、miR-199a-3p、miR-223-3p在诊断肝癌中的临床意义,以及分析与肝癌病理因素的关系。方法共收集42例肝癌、35例慢性活动性肝炎以及30例正常对照血清标本,应用DDPCR技术检测血清中4种miRNAs的表达量,化学发光法检测血清中AFP含量。结果肝癌血清中,miR-21、miR-223-3P、miR-199a-3p、miR-221的表达量分别为79.42±21.46、149.52±42.58、5.67±3.37、53.16±14.12copies/μl,表达上调的有miR-21、miR-223-3P和miR-221,三者分别与正常对照组比较差异有统计学意义(P<0.05),其中miR-221较慢性活动性肝炎和正常对照组差异均有统计学意义(P<0.05);三者ROC曲线分析敏感度、特异性和曲线下面积分别为miR-21(85.6%、74.9%、0.811)、miR-223-3P(73.2%、71.6%、0.709)和miR-221(76.3%、73.6%、0.761),三者联合检测结果明显提高(93.6%、92.9%、0.935);Spearman相关分析显示,血清中miR-221的表达量与肝癌的TNM分级有关(P<0.05),而与患者性别、年龄、是否携带HBV病毒、AFP水平等无关(P>0.05)。结论血清miR-21、miR-223-3P和miR-221在肝癌患者中显著上升,与对照组比较差异有统计学意义(P<0.05),可能对肝癌的诊断和预后存在潜在的价值。

Objective To investigate the clinical significance of serum miR-21, miR-221, miR-199a-3p, miR-223-3p in the diagnosis of liver cancer, and the relationship between the analysis and the pathological factors of HCC. Methods Serum samples of 42 cases of liver cancer, 35 cases of chronic active hepatitis and 30 normal controls were collected. The expression of 4 kinds of miRNAs in serum was detected by DDPCR, and the content of AFP in serum was detected by chemiluminescence method. Results The expressions levels of miR-21, miR-223-3P, miR-199a-3p and miR-221 in liver cancer were 79.42±21.46,149.52±42.58,5.67±3.37 and 53.16±14.12copies/μl, respectively.The up-regulated expression were in miR21,miR-233-3P and miR-221.In the three groups,compared with the normal control group, the difference was statistically significant（P〈0.05）. As for miR-221, compared with the chronic active hepatitis group and the normal control group, the difference was statistically significant （P〈0.05）.Three ROC curve analysis of mir-21, miR-223-3 p and and miR-221 for analysis sensitivity and specificity showed that the area under the curve of miR-21 was 85.6%, 74.9%, 0.811,miR-223-3 p 73.2%, 71.6%, 0.709, and miR-221 76.3%, 73.6%, 0.761,The three combined detection results significantly increased （93.6%, 92.9%, 0.935）. Spearman correlation analysis showed that the expression of miR-221 in serum was relaend with liver cancer TNM classification （P〈0.05）, and was not related to patients＇ gender, age, level of AFP, carrying the HBV virus （P〉0.05）. Conclusion Serum miR-21, miR-223-3P and miR-221 increased significantly in HCC patients. Compared with the control group the difference was statistically significant （P〈0.05）. The diagnosis and prognosis of hepatocellular carcinoma may have potential value.