Geng Qing, Fan Tao, Zhang Boyou, Wang Wei, Xu Yao, Hu Hao
Department of Thoracic Surgery, Renmin Hospital of Wuhan University, 238 Jie Fang Rd, Wuhan, 430060, China.
Respir Res. 2014 Nov 25;15(1):149. doi: 10.1186/s12931-014-0149-3.
In order to find novel noninvasive biomarkers with high accuracy for the screening of early-stage non-small cell lung cancer (NSCLC), we investigate the predictive power of 5 microRNAs (miR-20a, miR-145, miR-21, miR223 and miR-221) as potential biomarkers in early-stage NSCLC.
In training set, 25 early-stage NSCLC patients and 25 matched healthy controls are included to assess the miRNA expression profile between early-stage NSCLC patients and healthy controls by real-time RT-PCR. We found that five of these miRNAs (miR-20a, miR-223, miR-21, miR-221 and miR-145) levels in NSCLC patients were significantly dysregulated compared with the healthy groups and thus were selected to validation set. Therefore, a validation experiment was further performed to investigate the potential predictive power of these five miRNAs based on 126 early-stage NSCLC patients, 42 NCPD patients and 60 healthy controls. The receiver operating characteristic (ROC) curves were generated for the five miRNAs.
ROC curve analyses suggested that these five plasma miRNAs could be promising biomarkers for NSCLC, with relatively high AUC values as follows: miR-20a, 0.89 with 95% CI of [0.85-0.93]; miR-223, 0.94 with 95% CI of [0.91-0.96]; miR-21, 0.77 with 95% CI of [0.71-0.83]; miR-155, 0.92 with 95% CI of [0.89-0.96]; miR-145, 0.77 with 95% CI of [0.71-0.83]. Stratified analyses indicated that plasma miR-20a, miR-223, miR-21 and miR-145 showed better predictive value in smokers than in non-smokers, while miR-155 might be more suitable for non-smokers. In addition, all of these five miRNAs could differentiate NSCLC from controls with a higher accuracy in advanced stage and squamous carcinoma subgroups.
In conclusion, our study suggested that five plasma miRNAs (miR-20a, miR-145, miR-21, miR-223 and miR-221) can be used as promising biomarkers in early screening of NSCLC. Nevertheless, further validation and optimizing improvement should be performed on larger sample to confirm our results.
为了寻找用于早期非小细胞肺癌（NSCLC）筛查的新型高精度无创生物标志物，我们研究了5种微小RNA（miR-20a、miR-145、miR-21、miR-223和miR-221）作为早期NSCLC潜在生物标志物的预测能力。
在训练组中，纳入25例早期NSCLC患者和25例匹配的健康对照，通过实时RT-PCR评估早期NSCLC患者与健康对照之间的miRNA表达谱。我们发现，与健康组相比，NSCLC患者中这5种miRNA（miR-20a、miR-223、miR-21、miR-221和miR-145）的水平显著失调，因此被选入验证组。因此，基于126例早期NSCLC患者、42例非癌性肺疾病（NCPD）患者和60例健康对照，进一步进行了验证实验，以研究这5种miRNA的潜在预测能力。为这5种miRNA绘制了受试者工作特征（ROC）曲线。
ROC曲线分析表明，这5种血浆miRNA可能是NSCLC的有前景的生物标志物，AUC值相对较高，如下所示：miR-20a，0.89，95%CI为[0.85-0.93]；miR-223，0.94，95%CI为[0.91-0.96]；miR-21，0.77，95%CI为[0.71-0.83]；miR-155，0.92，95%CI为[0.89-0.96]；miR-145，0.77，95%CI为[0.71-0.83]。分层分析表明，血浆miR-20a、miR-223、miR-21和miR-145在吸烟者中的预测价值优于非吸烟者，而miR-155可能更适用于非吸烟者。此外，这5种miRNA在晚期和鳞状癌亚组中均能以更高的准确性区分NSCLC与对照。
总之，我们的研究表明，5种血浆miRNA（miR-20a、miR-145、miR-21、miR-223和miR-221）可作为NSCLC早期筛查中有前景的生物标志物。然而，应在更大样本上进行进一步验证和优化改进以证实我们的结果。
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