Profiling Plasma MicroRNA in Nasopharyngeal Carcinoma with Deep Sequencing

BACKGROUND: The goal of this study was to establish a plasma microRNA profile by use of next-generation sequencing that could aid in assessment of patient prognosis in nasopharyngeal carcinoma (NPC). METHODS: Two panels of NPC patients and healthy controls (HCs) were recruited for this study. We used deep sequencing to screen plasma microRNAs. Differentially expressed microRNAs were verified by quantitative realtime PCR (qPCR). Kaplan-Meier survival analysis with the log-rank test was used to compare overall survival (OS) and progression-free survival (PFS) between groups. RESULTS: Twenty-three plasma miRNAs with differential expression levels were selected for qPCR analysis on an independent set including 100 NPC patients and 55 HCs. NPC patients with low concentrations of miR-483-5p and miR-103 had better prognosis for 5-year OS than those with high concentrations (87.5% vs 55.8%, P < 0.001; 80.9% vs 62.3%, P = 0.031). Those with low concentrations of miR-29a and let-7c had poorer prognosis (54.8% vs 82.8%, P = 0.002; 56.3% vs 84.6%, P = 0.001). A 3-signature miRNA integrated with clinical stage was further identified in an independent set. We calculated a prognostic index score and classified patients into low-, medium-, and high-risk groups. Five-year OS among the 3 groups was significantly different (90.9%, 66.7%, and 23.8%; P < 0.001). By multivariate analysis, a high-risk score was the most significantly unfavorable prognostic factor independent of other clinical variables (P < 0.001, hazard ratio = 15.1, 95% CI = 5.2-43.9). CONCLUSIONS: Differentially expressed plasma miRNAs as identified by next-generation sequencing can be helpful for predicting survival in NPC patients. (C) 2014 American Association for Clinical Chemistry