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

Abstract

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.

• Authors: Jeff P Bruce, Angela B Y Hui, Wei Shi, Bayardo Perez-Ordonez, Ilan Weinreb, Wei Xu, Benjamin Haibe-Kains, Daryl M Waggott, Paul C Boutros, Brian O'Sullivan, John Waldron, Shao Hui Huang, Eric X Chen, Ralph Gilbert, Fei-Fei Liu
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 6 Pg. 4537-50 (Feb 28 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 25738365 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Area Under Curve
• Carcinoma
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• MicroRNAs (analysis)
• Middle Aged
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (genetics, pathology)
• ROC Curve
• Transcriptome
• Young Adult