南方医科大学学报

南方医科大学学报 ›› 2019, Vol. 39 ›› Issue (06): 705-.doi: 10.12122/j.issn.1673-4254.2019.06.12

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非小细胞肺癌早期诊断的潜在生物标志物：血浆miRNA-23a和miRNA-451

崔胜金，曹朝鹏，郭伟权，余蕙君，黄荣，吴云风   

  • 出版日期:2019-06-20 发布日期:2019-06-20

Plasma miRNA-23a and miRNA-451 as candidate biomarkers for early diagnosis of nonsmall cell lung cancer: a case-control study

  • Online:2019-06-20 Published:2019-06-20

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摘要： 目的研究血浆中miRNA23-a及miRNA-451 作为潜在生物标志物在非小细胞肺癌（NSCLC）中早期诊断的价值。方法 选取本院50例NSCLC病例和50例健康对照，通过实时荧光定量PCR（qRT-PCR）测定组织和血浆中miRNA23-a及miRNA-451 的表达水平，分析miRNA23-a及miRNA-451在组织和血浆中的表达差异及相关性。同时使用受试者工作特征曲线（ROC曲 线）和线下面积（AUC）评估miRNA23-a、miRNA-451及CEA在NSCLC中的诊断能力。通过瞬时转染技术，在NSCLC细胞系 A549 中分别抑制miRNA-23a 和miRNA-451 的表达，使用qRT-PCR 检测SPRY2 mRNA及MIF mRNA的表达水平。结果 miRNA-23a及miRNA-451在NSCLC组织中的表达与吸烟状态、肿瘤大小、淋巴结转移和TNM分期显著相关（P<0.05）。与对 照组相比，miRNA-23a在NSCLC患者的肿瘤组织和血浆中显著升高，而miRNA-451明显低于对照组。这2种miRNA的水平 在肿瘤组织与血浆中表现出相同的表达趋势，呈高度相关。ROC分析显示，miRNA-23a和miRNA-451较之传统的肿瘤标志物 CEA，AUCROC、灵敏度和特异度均显著高于后者（P<0.05）。当miRNA23-a及miRNA-451联合检测时，AUCROC/灵敏度/特异度均 得到改善，分别为0.900/78%/86%。在NSCLC细胞系A549中分别抑制miRNA-23a和miRNA-451的表达后，SPRY2 mRNA及 MIF mRNA表达水平显著升高。结论miRNA-23a和miRNA-451可用作NSCLC早期诊断的候选标志物，这2种标志物联合检 测对NSCLC诊断更有效。

Abstract: Objective To study the value of plasma miRNA23-a and miRNA-451 as potential biomarkers for early diagnosis of non-small cell lung cancer (NSCLC). Methods Fifty patients with NSCLC and 50 healthy control subjects were recruited for testing the plasma levels of miRNA23-a and miRNA-451 and their expression levels in the tumor tissues using qRT-PCR. The correlations of the plasma levels of miRNA23-a and miRNA-451 with their expressions in the tumor tissues were analyzed. The diagnostic power of CEA, miRNA23-a and miRNA-451 for NSCLC was evaluated using the receiver-operating characteristics (ROC) curves and the area under the ROC curves (AUC). In the NSCLC cell line A549, we tested the effect of inhibition of miRNA-23a and miRNA-451 on the expression levels of SPRY2 and MIF mRNA using qRT-PCR. Results The expression levels of miRNA-23a and miRNA-451 in NSCLC tissues was significantly associated with smoking, tumor size, lymph node metastasis and TNM stage (P<0.05). Compared with those in the control group, miRNA-23a level was significantly increased while miRNA-451 was significantly down-regulated in the tumor tissues and plasma of NSCLC patients. The plasma levels of miRNA-23a and miRNA-45 were strongly correlated with their expression levels in the tumor tissues. ROC analysis showed that for the diagnosis of NSCLC, the AUC, sensitivity and specificity of either miRNA-23a or miRNA-451 were significantly higher than those of CEA (P<0.05). The combination of miRNA23-a and miRNA-451 markedly improved the AUC (0.900), sensitivity (78%) and specificity (86%) for the diagnosis. In A549 cells, inhibition of miRNA23-a and miRNA-451 resulted in significantly increased expression levels of SPRY2 mRNA and MIF mRNA, respectively. Conclusions miRNA-23a and miRNA-451 can be used as potential biomarkers for early diagnosis of NSCLC, and their combined detection can be more effective for the diagnosis.