Identification of two microRNA signatures in whole blood as novel biomarkers for diagnosis of nasopharyngeal carcinoma
Identification of two microRNA signatures in whole blood as novel biomarkers for diagnosis of nasopharyngeal carcinoma
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鉴定全血中的两种 microRNA 特征作为诊断鼻咽癌的新型生物标志物
DOI：
10.1186/s12967-019-1923-2
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发表时间：
2019-06-03
影响因子：
7.4
通讯作者：
Guo, Ling
中科院分区：
文献类型：
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作者：
Wen, Wen;Mai, Shi-Juan;Guo, Ling
背景鼻咽癌的早期诊断是降低死亡率的关键。microRNAs（miRNAs）在肿瘤发生中发挥重要作用。因此，本研究的目的是确定诊断相关的循环miRNA签名的患者与NPC.MethodsTotal RNA提取从全血样本中获得的120例鼻咽癌患者，30例头颈部肿瘤（HNT），和30例健康受试者（HS），并检查通过使用自定义的微阵列。采用实时荧光定量逆转录聚合酶链反应（RT-PCR）对芯片检测到的4种miRNAs的表达水平进行验证。将120例NPC患者和30例HS患者随机分为训练组1和验证组1。应用微阵列显著性分析（SAM）技术，获得鼻咽癌患者全血中特异性miRNA表达谱。通过使用套索回归和自适应增强，在训练组-1中识别诊断特征，并在验证组-1中验证其准确性。采用同样的方法，在训练组2中筛选出一个可区分鼻咽癌与HNT和HS患者的特征，并在验证组2中进行验证。结果在117个差异表达的miRNAs中，有117个差异表达的miRNAs（上调和下调倍数变化≥ 1.5），其中8-miRNA标记在训练组-1诊断NPC的敏感性为96.43%，特异性为100%[曲线下面积（AUC）= 0.995]，在训练组-1诊断NPC的敏感性为86.11%，特异性为88.89（AUC = 0.941）。与传统的EB病毒（EBV）血清标志物相比，该标志物对鼻咽癌具有更高的特异性。此外，从164个差异表达的miRNA中建立了区分NPC与HNT和HS的16-miRNA标签（HNT-HS），诊断鼻咽癌和HNT-HS的准确率为100%（AUC = 1.000）训练组-2和87.04%验证组（AUC = 0.924）-2.结论本研究发现了两个miRNA标记，可用于鼻咽癌与HS的高准确性诊断和鉴别诊断，HNT患者这些miRNAs可能成为鼻咽癌新的血清学标志物和潜在的治疗靶点。
BackgroundEarly diagnosis is critical to reduce the mortality caused by nasopharyngeal carcinoma (NPC). MicroRNAs (miRNAs) are dysregulated and play important roles in carcinogenesis. Therefore, this study aimed to identify diagnostically relevant circulating miRNA signatures in patients with NPC.MethodsTotal RNA was extracted from whole blood samples obtained from 120 patients with NPC, 30 patients with head-neck tumors (HNT), and 30 healthy subjects (HSs), and examined by using a custom microarray. The expression levels of four miRNAs identified by using the microarray were validated with quantitative real-time reverse transcription polymerase chain reaction. The 120 patients with NPC and 30 HSs were randomly assigned to training group-1 and validation group-1, respectively. By using significance analysis of microarray (SAM), the specific miRNA expression profiles in whole blood from patients with NPC are obtained. By using lasso regression and adaptive boosting, a diagnostic signature was identified in training group-1, and its accuracy was verified in validation group-1. By using the same methods, another signature to distinguish patients with NPC from those with HNT and HSs was identified in training group-2 and confirmed in validation group-2.ResultsThere were 117 differentially expressed miRNAs (upregulated and downregulated fold change ≥ 1.5) between the patients with NPC and HSs, among which an 8-miRNA signature was identified with 96.43% sensitivity and 100% specificity [area under the curve (AUC) = 0.995] to diagnose NPC in training group-1 and 86.11% sensitivity and 88.89% specificity (AUC = 0.941) in validation group-1. Compared with traditional Epstein–Barr virus (EBV) seromarkers, this signature was more specific for NPC. Furthermore, a 16-miRNA signature to differentiate NPC from HNT and HS (HNT-HS) was established from 164 differentially expressed miRNAs, which diagnosed NPC and HNT-HS with 100% accuracy (AUC = 1.000) in training group-2 and 87.04% (AUC = 0.924) in validation group-2.ConclusionsThe present study identified two miRNA signatures for the highly accurate diagnosis and differential diagnosis of patients with NPC from HSs and patients with HNT. The identified miRNAs might represent novel serological biomarkers and potential therapeutic targets for NPC.