Department of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, China.
Nano-Bio-Chem Centre, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
BMC Cancer. 2019 Aug 28;19(1):843. doi: 10.1186/s12885-019-6037-y.
Recent studies reported that blood-based microRNAs (miRNAs) could detect cancers and predict prognosis have opened a new field of utilizing circulating miRNAs as cancer biomarkers. In this pilot study, we conducted for the first time, to our knowledge, the evaluation of the applicability of salivary miRNAs as novel biomarkers for nasopharyngeal carcinoma (NPC) detection.
Microarray miRNA expression profiling was performed on saliva samples from 22 newly diagnosed NPC patients and 25 healthy controls, and 12 significantly down-regulated miRNAs were selected for quantitative real-time-PCR (qRT-PCR) validation and further analysis. Their target genes enriched by gene ontology and pathway analysis were used to construct regulatory and interaction networks. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy.
Twelve dysregulated miRNAs screened by microarray that showed the same expression patterns with qRT-PCR analysis. Through bioinformatics analysis, the most prominent hub gene probably regulated by the 12 down-regulated miRNAs is found to be TP53. The ROC including the 12 miRNAs separated NPC patients from healthy controls with very high accuracy (areas under the receiver operating characteristic curve [AUC] = 0.999, sensitivity = 100.00%, specificity = 96.00%). Furthermore, if only six significantly dysregulated miRNAs were selected for the ROC analysis, the accuracy is still impressive (AUC = 0.941, sensitivity = 95.45%, specificity = 80.00%).
This study highlights the potential for salivary miRNAs as biomarkers for the detection of NPC. Meanwhile, differentially expressed miRNAs in saliva might play critical roles in NPC by regulating their target genes, which associated with some significant pathways, such as p53 signaling pathway.
最近的研究报告称,基于血液的 microRNAs(miRNAs)可用于检测癌症并预测预后,这为利用循环 miRNAs 作为癌症生物标志物开辟了新的领域。在这项初步研究中,我们首次评估了唾液 miRNAs 作为新型鼻咽癌(NPC)检测生物标志物的适用性。
对 22 例新诊断的 NPC 患者和 25 例健康对照者的唾液样本进行 microarray miRNA 表达谱分析,选择 12 个显著下调的 miRNA 进行定量实时 PCR(qRT-PCR)验证和进一步分析。通过基因本体和通路分析富集其靶基因,构建调控和相互作用网络。通过计算受试者工作特征分析(ROC)和逻辑回归来评估判别准确性。
微阵列筛选出 12 个失调 miRNA,与 qRT-PCR 分析显示出相同的表达模式。通过生物信息学分析,发现由这 12 个下调 miRNA 调控的最显著的枢纽基因可能是 TP53。包含这 12 个 miRNA 的 ROC 曲线可非常准确地将 NPC 患者与健康对照者区分开来(ROC 曲线下面积[AUC] = 0.999,灵敏度 = 100.00%,特异性 = 96.00%)。此外,如果仅选择 6 个显著失调 miRNA 进行 ROC 分析,准确性仍然令人印象深刻(AUC = 0.941,灵敏度 = 95.45%,特异性 = 80.00%)。
本研究强调了唾液 miRNAs 作为 NPC 检测生物标志物的潜力。同时,唾液中差异表达的 miRNAs 通过调控其靶基因可能在 NPC 中发挥关键作用,这些靶基因与一些重要的通路有关,如 p53 信号通路。