血浆 miR-199a-5p 与 miR-200c-3p在胃腺癌中的临床应用

摘要

目的：探讨胃腺癌患者血浆中miR-199a-5p、miR-200c-3p的表达及其对胃腺癌诊断和预后判断的临床意义。方法采用病例对照研究方法，对2013年9月至2014年7月在南京医科大学附属肿瘤医院住院的47例胃腺癌患者及50名健康对照者进行研究，应用实时荧光定量PCR技术（TaqMan探针法）检测血浆中miR-199a-5p和miR-200c-3p的表达水平，分析其与年龄、性别、肿瘤定位、大小、分化程度、TNM分期、淋巴结转移等病理参数的关系，并比较30例胃癌根治术前及术后6～8天血浆中 miRNAs 表达的变化情况；应用受试者工作特征曲线（ receiver operating characteristic， ROC）分析miRNAs的表达对胃癌诊断的灵敏度和特异性。采用SPSS20.0统计学软件进行统计分析，正态分布的计量资料采用t检验，术前术后对比采用配对t检验，多组间比较采用单因素方差分析。结果 miR-199a-5p在胃癌患者血浆中的相对表达量为（1.05±0.22），与对照组（26.80±8.38）相比，显著降低（t＝3.058，P＝0.003），且与淋巴结转移（F＝4.725，P＝0.029）及肿瘤分化程度（F＝3.854，P＝0.032）相关。而miR-200c-3p在胃癌患者血浆中相对表达量为（15.15±3.02），与对照组（3.39±0.87）相比，显著升高（t＝－2.854，P＝0.006）。 MiR-199a-5p在术后表达增高（t＝－3.814，P＝0.001）而miR-200c-3p在术后表达降低（t＝2.978，P＝0.006）。 ROC曲线分析表明血浆miR-199a-5p、miR-200c-3p、miR-199a-5p和miR-200c-3p曲线下面积（ AUC）分别是0.692、0.792、0.798；三者的敏感性分别是87％、97％、92.5％；特异性分别是43％、54％、65％。结论 MiR-199a-5p和miR-200c-3p对胃腺癌的联合检测具有较高的灵敏度和特异性。（中华检验医学杂志，2015，38：402-406）%Objective To explore the relative expression of plasma miR-199a-5p and miR-200c-3p in gastric adenocarcinoma cancer(GAC) patients and its clinical value.Methods Case-control study was used in this research.The relative expression of plasma miR-199a-5p and miR-200c-3p from 47 GAC patients and 50 healthy controls were determined by RT-PCR ( TaqMan Probe method).Meanwhile, the association with age, gender, tumor location, size, degree of differentiation, TNM stage, lymph node metastasis and other clinical pathological parameters were analyzed.The expression of these two miRNAs in plasma of 30 GAC patients during preoperation was compared with their expression 6-8 days after radical surgery.The sensitivity and specificity of plasma miRNAs expression for the diagnosis of GAC were analyzed using the receiver operating characteristic ( ROC ) curve.SPSS20.0 statistical software was used for statistical analysis.T-test, paired t-test and one-factor ANOVA were used for normal distribution of quantitative data.Results The plasma level of miR-199a-5p in GAC patients was significantly lower(1.05 ±0.22) (t =3.058,P =0.003), while miR-200c-3p was significantly higher(15.15 ±3.02) (t =-2.854,P=0.006), when they were compared with those in controls(26.80 ±8.38, 3.39 ±0.87).Low miR-199a-5p expression in GAC patients were associated with lymph node metastasis ( F =4.725, P =0.029) and the differentiation degree of gastric cancer(F=3.854,P=0.032).The relative expression of miR-199a-5p in postoperative plasma was significantly increased(t=-3.814,P=0.001), but the relative expression of miR-200c-3p was significantly reduced when compared to the preoperative samples(t=2.978, P=0.006).Area under the ROC curve of miR-199a-5p, miR-200c-3p and combined miR-199a-5p and miR-200c-3p were 0.692, 0.792 and 0.798, the sensitivity and specificity were 87%,97%,92.5% and 43%,54%, 65%, respectively.Conclusion Combined detection of miR-199a-5p and miR-200c-3p in plasma has a higher sensitivity and specificity than the conventional tumor marker CEA and CA19-9, and may be a useful combination for gastric cancer diagnosis.