Department of Electronic Engineering, City University of Hong Kong, Hong Kong, China.
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China.
J Biomed Sci. 2018 Feb 19;25(1):16. doi: 10.1186/s12929-018-0417-5.
Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer, with diverse molecular characteristics and clinical outcomes. This study aims to dissect the molecular heterogeneity of NPC, followed by the construction of a microRNA (miRNA)-based prognostic model for prediction of distant metastasis.
We retrieved two NPC datasets: GSE32960 and GSE70970 as training and validation cohorts, respectively. Consensus clustering was employed for cluster discovery, and support vector machine was used to build a classifier. Finally, Cox regression analysis was applied to constructing a prognostic model for predicting risk of distant metastasis.
Three NPC subtypes (immunogenic, classical and mesenchymal) were identified that are molecularly distinct and clinically relevant, of which mesenchymal subtype (~ 36%) is associated with poor prognosis, characterized by suppressing tumor suppressor miRNAs and the activation of epithelial--mesenchymal transition. Out of the 25 most differentially expressed miRNAs in mesenchymal subtype, miR-142, miR-26a, miR-141 and let-7i have significant prognostic power (P < 0.05).
We proposed for the first time that NPC can be stratified into three subtypes. Using a panel of 4 miRNAs, we established a prognostic model that can robustly stratify NPC patients into high- and low- risk groups of distant metastasis.
鼻咽癌（NPC）是一种具有高度侵袭性和转移性的癌症，具有多种分子特征和临床结局。本研究旨在剖析 NPC 的分子异质性，并构建基于 microRNA（miRNA）的预后模型，以预测远处转移。
我们检索了两个 NPC 数据集：GSE32960 和 GSE70970，分别作为训练和验证队列。采用共识聚类进行聚类发现，支持向量机用于构建分类器。最后，应用 Cox 回归分析构建预测远处转移风险的预后模型。
鉴定出三种 NPC 亚型（免疫型、经典型和间质型），它们在分子上是不同的，在临床上也是相关的，其中间质型（约 36%）与预后不良相关，其特征是抑制肿瘤抑制 miRNA 和上皮-间质转化的激活。在间质型中差异表达最显著的 25 个 miRNA 中，miR-142、miR-26a、miR-141 和 let-7i 具有显著的预后预测能力（P<0.05）。
我们首次提出 NPC 可以分为三种亚型。我们使用一组 4 个 miRNA，建立了一个预后模型，可以稳健地将 NPC 患者分为远处转移的高风险和低风险组。
