Yang Jin-shan, Li Bao-jian, Lu Hua-wei, Chen Yu, Lu Chuan, Zhu Rui-xia, Liu Si-hai, Yi Qing-ting, Li Jing, Song Chun-hui
Department of Oncology, Central Hospital of Zaozhuang Mineral Group, Qilianshan Road, Zaozhuang, 277800, China,
Tumour Biol. 2015 Apr;36(4):3035-42. doi: 10.1007/s13277-014-2938-1. Epub 2014 Dec 14.
Lung cancer, predominantly by non-small cell lung cancer (NSCLC), is the leading cause of cancer-related deaths over the world. Late diagnosis is one of important reasons for high mortality rate in lung cancer. Current diagnostic approaches have disadvantages such as low accuracy, high cost, invasive procedure, etc. MicroRNAs were previously proposed as promising novel biomarkers in cancer screening. In this study, we evaluated the predictive power of four candidate miRNAs in NSCLC detection. Our study involved 152 NSCLC patients and 300 healthy controls. Blood samples were obtained from the total 452 subjects. After miRNA extraction from serum, the expression of miRNAs in cases and controls were quantified by qRT-PCR and normalized to the level of U6 small RNA. Statistical analyses were performed to compare miRNA levels between cases and controls. Stratified analyses were employed to compare miRNA levels in NSCLC patients with different clinical characteristics. Serum miR-148a, miR-148b, and miR-152 were significantly downregulated in NSCLC patients. However, overexpression of serum miR-21 was observed in NSCLC patients. The combination of four candidate miRNAs exhibited the highest predictive accuracy in NSCLC screening compared with individual miRNAs (AUC = 0.97). Low level of miRNA-148/152 members may associate with advanced stage, large tumor size, malignant cell differentiation, and metastasis. High expression of miR-21 was possibly correlated with large size tumor and advanced cancer stage. Our results showed the dysregulation of miR-148/152 family and miR-21 in NSCLC patients. Hence, the four candidate miRNAs have great potential to serve as promising novel biomarkers in NSCLC screening. Further large-scale studies are needed to validate our results.
肺癌，主要是非小细胞肺癌（NSCLC），是全球癌症相关死亡的主要原因。晚期诊断是肺癌死亡率高的重要原因之一。目前的诊断方法存在准确性低、成本高、侵入性操作等缺点。微小RNA（MicroRNAs）此前被认为是癌症筛查中很有前景的新型生物标志物。在本研究中，我们评估了四种候选微小RNA在NSCLC检测中的预测能力。我们的研究纳入了152例NSCLC患者和300名健康对照。从总共452名受试者中采集血样。从血清中提取微小RNA后，通过qRT-PCR对病例组和对照组中微小RNA的表达进行定量，并将其标准化为U6小RNA的水平。进行统计分析以比较病例组和对照组之间的微小RNA水平。采用分层分析比较具有不同临床特征的NSCLC患者中的微小RNA水平。NSCLC患者血清中的miR-148a、miR-148b和miR-152显著下调。然而，在NSCLC患者中观察到血清miR-21过表达。与单个微小RNA相比，四种候选微小RNA的组合在NSCLC筛查中表现出最高的预测准确性（AUC = 0.97）。miRNA-148/152成员水平低可能与晚期、肿瘤体积大、恶性细胞分化和转移有关。miR-21高表达可能与肿瘤体积大及癌症晚期相关。我们的结果显示NSCLC患者中miR-148/152家族和miR-21失调。因此，这四种候选微小RNA有很大潜力成为NSCLC筛查中很有前景的新型生物标志物。需要进一步的大规模研究来验证我们的结果。
