Molecular subtyping of nasopharyngeal carcinoma (NPC) and a microRNA-based prognostic model for distant metastasis

• Published in: Journal of biomedical science Vol. 25; no. 1; p. 16
• Main Authors: Zhao, Lan, Fong, Alvin H W, Liu, Na, Cho, William C S
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19-02-2018; BioMed Central; BMC
• Subjects: Cancer metastasis; Carcinoma - diagnosis; Carcinoma - genetics; Carcinoma - secondary; Complications and side effects; Consensus clustering; Cox regression model; Diagnosis; Distant metastasis; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic - genetics; Health aspects; Humans; Male; MicroRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; Models, Genetic; Molecular subtyping; Nasopharyngeal cancer; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - diagnosis; Nasopharyngeal Neoplasms - genetics; Nasopharyngeal Neoplasms - secondary; Prognosis; Distant metastasis; Nasopharyngeal carcinoma; microRNA; Cox regression model; Molecular subtyping; Consensus clustering
• ISSN: 1423-0127; 1021-7770; 1423-0127
• 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.