微小RNA在胰腺癌患者血浆中的表达情况及临床意义

Expression and clinical significance of plasma small RNA in patients with pancreatic cancer

目的探讨微小RNA（miRNA）在胰腺癌患者血浆中的表达情况及临床意义。方法采用实时定量PCR方法检测30例胰腺癌和26例健康志愿者血浆中miR-21、miR-210、miR-155、miR．20a、miR-25和miR-196a的表达水平，并分析miR-21、miR-210、miR-155、miR-20a、miR-25和miR-196a与CA19-9联合诊断胰腺癌的价值。结果miR-21、miR-210、miR-155、miR-20a、miR-25和miR-196a在胰腺癌患者血浆中的中位表达水平分别为1．65×10^6、5．98×10^4、2．83×10^3、3．47×10^6、2．76×10^6和1．03×10^3 copies／μl，正常对照者分别为4．08×10^5、2．54×10^4、8．55×10^2、1．79×10^6、9．32×10^5和4．67×10^2 copies／μl，差异有统计学意义（P〈0．05）。miR-21、miR-210、miR-155、miR-20a、miR-25和miR-196a的受试者工作特征曲线（ROC曲线）下面积分别为0．893、0．810、0．820、0．766、0．816和0．729，miR-21的诊断价值最高。miR-155与miR-25联合诊断胰腺癌的ROC曲线下面积为0．913（95％口为0．838～0．988），明显优于单独miR-155和miR-25的诊断价值。miR-210与CA19-9、miR-25与CA19-9联合诊断胰腺癌的ROC曲线下面积分别为0．960（95％凹为0～1．0）和0．942（95％CI为0．876～1．0），优于单独CA19-9的ROC曲线下面积（0．862，95％CI为0．748～0．975）。miR-210、miR-25分别与CA19-9联合时诊断的灵敏度和准确率均明显升高。结论miR-21、miR-155、miR-25和miR-210对胰腺癌的诊断价值值得进一步研究。

Objective The aim of this study was to identify six miRNAs expressed in plasma of patients with pancreatic cancer （PCa） and analyze their value as a diagnostic index of pancreatic cancer. Methods Plasma total RNAs were extraeted from 30 PCa patients and 26 normal controls, and the abundance of six microRNAs was measured using real-time PCR. The possibility to combine them with CA19-9 as diagnostic biomarkers was analyzed. Results The expression level of miR-21, miR-210, miR- 155, miR-20a, miR-25 and miR-196a in plasma of patients with pancreatic cancer were 1.65 × 10^6, 5.98× 10^4, 2.83 × 10^3 , 3.47 × 10^6, 2.76 × 10^6, and 1.03 × 10^3 （ copies/μl） , while the normal controls were 4.08 ×10^5, 2.54 × 10^4, 8.55 × 10^2, 1.79 × 10^6, 9.32 × 10^5 , and 4.67 ×10^2 （copies/ixl） , respectively, with a significant difference between the two groups （ P 〈 0.05 ）. The areas under the ROC curve of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a were 0. 893, 0. 810, 0. 820, 0. 766, 0. 816 and 0.729, respectively. MiR-21 had the highest diagnostic value when it was used as diagnostic marker alone. The combination of miR-155 and miR-25 was more effective to distinguish PCa from normal than to be used alone, and the area under the ROC curve was 0. 913 （95% CI 0. 838-0. 988 ）. When CA199 associated with miR -210 and miR-25, respectively, the areas under the ROC curves were 0.96 （95% CI was 0-1.0）and 0.942（95% CI was 0. 876-1.0） , which were higher than CA199 alone （0. 862,95% CI was 0. 748- 0. 975 ）. There was a high improvement in diagnostic sensitivity and accuracy when miR-210 and miR-25were combind with CA19-9, respectively. Conclusions Plasma miR-21, miR-155, miR-25, miR-210 have diagnostic value for pancreatic cancer, and deserve further study.