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

Nan Fang Yi Ke Da Xue Xue Bao. 2019 Jun 30;39(6):705-711. doi: 10.12122/j.issn.1673-4254.2019.06.12.
[Article in Chinese]

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.

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。

Keywords: Biomarker; miRNA-23a; miRNA-451; non-small cell lung cancer.

MeSH terms

  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Case-Control Studies
  • Early Detection of Cancer
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lung Neoplasms* / genetics
  • Membrane Proteins
  • MicroRNAs
  • ROC Curve

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • MicroRNAs
  • SPRY2 protein, human

Grants and funding

广东省自然科学基金(2018A0303130119)