Fan Lihong, Qi Huiwei, Teng Junliang, Su Bo, Chen Hao, Wang Changhui, Xia Qing
Department of Respiration, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, 507 Zhengmin Road, Shanghai, 200433, People's Republic of China.
Tumour Biol. 2016 Jun;37(6):7777-84. doi: 10.1007/s13277-015-4608-3. Epub 2015 Dec 22.
Circulating microRNAs (miRNAs) are potential noninvasive biomarkers for cancer detection. We used preoperative serum samples from non-small cell lung cancer (NSCLC) patients and healthy controls to investigate whether serum levels of candidate miRNAs could be used as diagnostic biomarkers in patients with resectable NSCLC and whether they were associated with clinicopathologic characteristics. We initially detected expression of 12 miRNAs using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in preoperative serum samples of 94 NSCLC patients and 58 healthy controls. We further validated our results using the fluorescence quantum dots liquid bead array for differentially expressed miRNAs in serum samples of 70 NSCLC patients and 54 healthy controls. Receiver operating characteristic (ROC) analysis was performed to select the best diagnostic miRNA cutoff value. A predictive model of miRNAs for NSCLC was derived by multivariate logistic regression. We found that five serum miRNAs (miR-16-5p, miR-17b-5p, miR-19-3p, miR-20a-5p, and miR-92-3p) were significantly downregulated in NSCLC, while miR-15b-5p was significantly upregulated (p < 0.05). Multivariate logistic regression analysis revealed that miR-15b-5p, miR-16-5p, and miR-20a-5p expression were independent diagnostic factors for the identification of patients with NSCLC after adjustment for patient's age and sex. In addition, the expression of serum miR-106-5p was higher in stage I than in stages IIa-IIIb, and no significant association was observed between expression of miRNAs and other variables including pathological type, tumor size, and lymph nodes status. Six serum miRNAs could potentially serve as noninvasive diagnostic biomarkers for resectable NSCLC. The predictive model combining miR-15b-5p, miR-16-5p, and miR-20a-5p was the best diagnostic approach.
循环微RNA(miRNA)是癌症检测中潜在的非侵入性生物标志物。我们使用非小细胞肺癌(NSCLC)患者和健康对照者的术前血清样本,研究候选miRNA的血清水平是否可作为可切除NSCLC患者的诊断生物标志物,以及它们是否与临床病理特征相关。我们首先在94例NSCLC患者和58例健康对照者的术前血清样本中,使用定量逆转录聚合酶链反应(qRT-PCR)检测了12种miRNA的表达。我们进一步使用荧光量子点液珠阵列对70例NSCLC患者和54例健康对照者的血清样本中差异表达的miRNA进行验证。进行受试者操作特征(ROC)分析以选择最佳诊断miRNA临界值。通过多因素逻辑回归得出NSCLC的miRNA预测模型。我们发现,5种血清miRNA(miR-16-5p、miR-17b-5p、miR-19-3p、miR-20a-5p和miR-92-3p)在NSCLC中显著下调,而miR-15b-5p显著上调(p<0.05)。多因素逻辑回归分析显示,在对患者年龄和性别进行校正后,miR-15b-5p、miR-16-5p和miR-20a-5p的表达是识别NSCLC患者的独立诊断因素。此外,血清miR-106-5p的表达在I期高于IIa-IIIb期,且未观察到miRNA表达与包括病理类型、肿瘤大小和淋巴结状态在内的其他变量之间存在显著关联。六种血清miRNA可能作为可切除NSCLC的非侵入性诊断生物标志物。结合miR-15b-5p、miR-16-5p和miR-20a-5p的预测模型是最佳诊断方法。