Clinical Research Papers:
Identification of a microRNA signature associated with risk of distant metastasis in nasopharyngeal carcinoma
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Jeff P. Bruce1,2, Angela B. Y. Hui3, Wei Shi1, Bayardo Perez-Ordonez4, Ilan Weinreb4, Wei Xu5, Benjamin Haibe-Kains1,2, Daryl M. Waggott3, Paul C. Boutros2,6,7, Brian O’Sullivan8,9, John Waldron8,9, Shao Hui Huang8,9, Eric X. Chen10, Ralph Gilbert11, Fei-Fei Liu1,2,8,9
1Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
2Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
3Department of Medicine, Stanford University, Stanford, CA, United States
4Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
5Division of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
6Informatics and Biocomputing Program, Ontario Institute for Cancer Research, Toronto, ON, Canada
7Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
8Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
9Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
10Division of Medical Oncology, University of Toronto, Toronto, ON, Canada
11Department of Otolaryngology, University of Toronto, Toronto, ON, Canada
Fei-Fei Liu, e-mail: [email protected]
Keywords: microRNA, Nasopharyngeal Carcinoma, Distant Metastasis, Prognosis
Received: November 19, 2014 Accepted: December 21, 2014 Published: January 23, 2015
Despite significant improvement in locoregional control in the contemporary era of nasopharyngeal carcinoma (NPC) treatment, patients still suffer from a significant risk of distant metastasis (DM). Identifying those patients at risk of DM would aid in personalized treatment in the future. MicroRNAs (miRNAs) play many important roles in human cancers; hence, we proceeded to address the primary hypothesis that there is a miRNA expression signature capable of predicting DM for NPC patients.
Methods and results
The expression of 734 miRNAs was measured in 125 (Training) and 121 (Validation) clinically annotated NPC diagnostic biopsy samples. A 4-miRNA expression signature associated with risk of developing DM was identified by fitting a penalized Cox Proportion Hazard regression model to the Training data set (HR 8.25; p < 0.001), and subsequently validated in an independent Validation set (HR 3.2; p = 0.01). Pathway enrichment analysis indicated that the targets of miRNAs associated with DM appear to be converging on cell-cycle pathways.
This 4-miRNA signature adds to the prognostic value of the current “gold standard” of TNM staging. In-depth interrogation of these 4-miRNAs will provide important biological insights that could facilitate the discovery and development of novel molecularly targeted therapies to improve outcome for future NPC patients.
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