Identification of a microRNA signature associated with risk of distant metastasis in nasopharyngeal carcinoma

摘要: // Jeff P. Bruce 1, 2 , Angela B. Y. Hui 3 Wei Shi 1 Bayardo Perez-Ordonez 4 Ilan Weinreb Xu 5 Benjamin Haibe-Kains Daryl M. Waggott Paul C. Boutros 2, 6, 7 Brian O’Sullivan 8, 9 John Waldron Shao Huang Eric X. Chen 10 Ralph Gilbert 11 Fei-Fei Liu Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada Department of Medical Biophysics, Medicine, Stanford University, Stanford, CA, United States Pathology, Division Biostatistics, 6 Informatics and Biocomputing Program, Ontario Institute for Research, Pharmacology Toxicology, 8 Radiation Oncology, Otolaryngology, Correspondence to: Liu, e-mail: Fei-Fei.Liu@rmp.uhn.on.ca Keywords: microRNA, Nasopharyngeal Carcinoma, Distant Metastasis, Prognosis Received: November 19, 2014      Accepted: December 21, Published: January 23, 2015 ABSTRACT Purpose Despite significant improvement in locoregional control the contemporary era nasopharyngeal carcinoma (NPC) treatment, patients still suffer from a risk distant metastasis (DM). Identifying those at DM would aid personalized treatment future. MicroRNAs (miRNAs) play many important roles human cancers; hence, we proceeded to address primary hypothesis that there is miRNA expression signature capable predicting NPC patients. Methods results The 734 miRNAs was measured 125 (Training) 121 (Validation) clinically annotated diagnostic biopsy samples. A 4-miRNA associated with developing identified by fitting penalized Cox Proportion Hazard regression model Training data set (HR 8.25; p < 0.001), subsequently validated an independent Validation 3.2; = 0.01). Pathway enrichment analysis indicated targets appear be converging on cell-cycle pathways. Conclusions This adds prognostic value current “gold standard” TNM staging. In-depth interrogation these 4-miRNAs will provide biological insights could facilitate discovery development novel molecularly targeted therapies improve outcome future