血清miRNA作为胃癌早期诊断标记物的初步研究

Study on Serum miRNAs as Biomarkers for Early Diagnosis of Gastric Cancer

背景:已有研究发现部分血清miRNA与胃癌密切相关,但对早期胃癌的研究较少见。目的:探讨血清miR-1、miR-20a、miR-27a、miR-34a、miR-423-5p表达在胃癌尤其是早期胃癌诊断中的价值。方法:采用qRT-PCR法检测180例胃癌患者(包括149例进展期胃癌和31例早期胃癌)、49例癌前变化患者、57名健康对照者的血清miR-1、miR-20a、miR-27a、miR-34a、miR-423-5p表达。采用ROC曲线判断miRNA的诊断敏感性和特异性。结果:胃癌患者血清miR-1、miR-20a、miR-34a、miR-423-5p表达显著升高(P<0.05),ROC曲线下面积(AUC)分别为0.894 9、0.814 8、0.644 8、0.589 7,四者联合的AUC为0.921 1,敏感性和特异性分别为85.8%和83.3%。早期胃癌中miR-1和miR-20a的表达明显升高(P<0.05),AUC分别为0.813 8和0.774 2,两者联合的AUC为0.865 3,敏感性和特异性分别为80.5%和83.6%。进展期胃癌中miR-1的表达显著高于早期胃癌(P=0.012 1),且术后表达明显降低(P=0.018 5)。结论:miR-1、miR-20a、miR-34a、miR-423-5p可作为肿瘤标记物对胃癌进行诊断,miR-1、miR-20a可作为诊断早期胃癌的标记物。

Background： Recently studies showed that some serum miRNAs are closely related to gastric cancer （ GC ） , but studies on early GC are rare. Aims： To investigate the values of serum miRNAs （miR-1, miR-20a, miR-27a, miR-34a, miR-423-Sp） for diagnosis of GC, especially early GC. Methods： qRT-PCR was used to detect expressions of serum miRNAs （miR-1, miR-20a, miR-27a, miR-34a, miR-423-5p） in 180 patients with GC （including 149 advanced GC and 31 early GC）, 49 patients with precancerous change and 57 controls. ROC curve was used to evaluate the sensitivity and specificity of miRNAs. Results： Expressions of serum miR-1, miR-20a, miR-34a and miR-423-5p in GC patients were significantly increased （P 〈 0. 05） ; area under ROC curve （AUC） was 0. 894 9, 0. 814 8, 0. 644 8, 0. 589 7, respectively. AUC of these 4 combined miRNAs was 0. 921 1 ; sensitivity and specificity of combined miRNAs were 85.8% and 83.3% , respectively. Expressions of miR-I and miR-20a in early GC were significantly increased （P 〈0.05） , AUC were 0. 813 8 and 0. 774 2, respectively. AUC of combined miRNAs was 0. 865 3 ; sensitivity and specificity of combined miRNAs were 80.5% and 83.6% , respectively. Serum level of miR-1 was significantly higher in advanced GC patients than in early GC patients （P = 0. 012 1 ）, and was significantly decreased after surgery （P = 0. 018 5 ）. Conclusions： miR-1, miR-20a, miR-34a and miR-423-Sp may be used as potential biomarkers for the diagnosis of GC, especially miR- 1 and miR-20a which could be used for diagnosis of early GC.