Genome-wide study of salivary microRNAs as potential noninvasive biomarkers for detection of nasopharyngeal carcinoma
Genome-wide study of salivary microRNAs as potential noninvasive biomarkers for detection of nasopharyngeal carcinoma
复制标题
唾液 microRNA 作为鼻咽癌检测的潜在非侵入性生物标志物的全基因组研究
DOI：
10.1186/s12885-019-6037-y
复制
发表时间：
2019
期刊：
影响因子：
3.8
通讯作者：
Shen Ye
中科院分区：
文献类型：
--
作者：
Wu Lirong;Zheng Kexiao;Yan Cheng;Pan Xuan;Liu Yatian;Liu Juying;Wang Feijiang;Guo Wenjie;He Xia;Li Jiong;Shen Ye
最近的研究表明，基于血液的microRNAs(MiRNAs)可以检测癌症和预测预后，为利用循环中的miRNAs作为癌症生物标志物开辟了一个新的领域。在这项初步研究中，我们首次对唾液miRNAs作为新的鼻咽癌生物标志物的适用性进行了评估。方法对22例新诊断的鼻咽癌患者和25名健康对照的唾液样本进行微阵列miRNA表达谱分析，并选择12个表达显著下调的miRNAs进行定量实时聚合酶链式反应(qRT-PCR)验证和进一步分析。利用基因本体论和通径分析丰富的靶基因构建调控网络和相互作用网络。结果基因芯片筛选出12个表达异常的miRNAs，其表达模式与qRT-PCR分析结果一致。通过生物信息学分析，发现最显著的可能受12个下调的miRNAs调控的Hub基因是TP53。包括12个miRNA在内的ROC以非常高的准确率区分鼻咽癌患者和健康对照组(受试者工作特征曲线下面积[AuC] = 0.999，敏感性 = 100.00%，特异性 = 96.00%)。此外，如果仅选择6个显著异常的miRNAs进行鼻咽癌分析，其准确性仍然令人印象深刻(AUC = 0.941，敏感性 = 95.45%，特异性 = 80.00%)。结论本研究强调了唾液miRNA作为鼻咽癌生物标志物的潜力。同时，唾液中差异表达的miRNAs可能通过调控靶基因在鼻咽癌中发挥关键作用，这些基因与一些重要的信号转导途径有关，如P53信号通路。
BackgroundRecent 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.MethodsMicroarray 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.ResultsTwelve 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%).ConclusionsThis 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.