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

PURPOSE: 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....

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Detalles Bibliográficos
Autores principales: Bruce, Jeff P., Hui, Angela B. Y., Shi, Wei, Perez-Ordonez, Bayardo, Weinreb, Ilan, Xu, Wei, Haibe-Kains, Benjamin, Waggott, Daryl M., Boutros, Paul C., O'Sullivan, Brian, Waldron, John, Huang, Shao Hui, Chen, Eric X., Gilbert, Ralph, Liu, Fei-Fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414210/
https://www.ncbi.nlm.nih.gov/pubmed/25738365
Descripción
Sumario:PURPOSE: 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. CONCLUSIONS: 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.