Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Cancer Sci. 2021 Jun;112(6):2393-2404. doi: 10.1111/cas.14883. Epub 2021 Apr 5.
The microRNAs (miRNAs) in circulating small extracellular vesicles (sEVs) have been suggested as potential biomarkers in cancer diagnosis. This study was designed to evaluate the circulating sEV-derived miRNAs as biomarkers for the diagnosis of nasopharyngeal carcinoma (NPC). We compared the miRNA profiles in plasma-derived sEVs between 16 patients with NPC and 5 healthy controls (HCs). A distinct set of miRNAs that were differentially expressed between patients with NPC and HCs was determined by means of integrative bioinformatics approaches. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis revealed that the target genes of the differentially expressed miRNAs (DEMs) were mainly involved in cancer-associated signaling pathways. Seven representative DEMs were selected and further validated in an additional 60 patients with NPC and 40 HCs using quantitative reverse-transcription PCR analysis (qRT-PCR). Receiver operating characteristic (ROC) curve analysis was used to assess the accuracy of the sEV-miRNA-based model for diagnosis. The 3 miRNA-based model, comprising miR-134-5p, miR-205-5p, and miR-409-3p, showed good discriminating power with an area under the curve (AUC) value of 0.88 in the training set and 0.91 in the validation set. Furthermore, the diagnostic model had an excellent classification ability to distinguish patients with NPC at different clinical stages or Epstein-Barr virus infection status from HCs. In conclusion, our findings indicated that sEV-derived miRNA levels were altered in the plasma of patients with NPC in comparison with those in HCs. The model based on the 3 sEV-derived miRNAs could potentially act as an alternative or complementary approach for diagnosing NPC.
循环中小细胞外囊泡(sEVs)中的 microRNAs(miRNAs)已被认为是癌症诊断中的潜在生物标志物。本研究旨在评估循环 sEV 衍生的 miRNAs 作为鼻咽癌(NPC)诊断的生物标志物。我们比较了 16 例 NPC 患者和 5 例健康对照(HC)之间血浆来源的 sEV 中的 miRNA 谱。通过综合生物信息学方法确定了 NPC 患者和 HCs 之间差异表达的 miRNA(DEMs)的一组独特的 miRNA。京都基因与基因组百科全书(KEGG)富集途径分析显示,差异表达 miRNA 的靶基因主要参与与癌症相关的信号通路。选择了 7 个有代表性的 DEMs,并使用定量逆转录 PCR 分析(qRT-PCR)在另外 60 例 NPC 患者和 40 例 HCs 中进一步验证。使用接收器操作特性(ROC)曲线分析评估基于 sEV-miRNA 的模型对诊断的准确性。由 miR-134-5p、miR-205-5p 和 miR-409-3p 组成的 3 个 miRNA 模型在训练集中的 AUC 值为 0.88,在验证集中的 AUC 值为 0.91,显示出良好的区分能力。此外,该诊断模型具有极好的分类能力,能够区分 NPC 不同临床阶段或 Epstein-Barr 病毒感染状态的患者与 HCs。总之,我们的研究结果表明,与 HCs 相比,NPC 患者血浆中的 sEV 衍生 miRNA 水平发生了改变。基于 3 个 sEV 衍生 miRNA 的模型可能是诊断 NPC 的一种替代或补充方法。