Liquid biopsy profiling of serum exosomal miRNAs enables early prediction of distant metastasis in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) has an excellent locoregional control rate following definitive chemoradiotherapy (CRT) while distant metastasis (DM) remained the major failure pattern. We examined exosomal miRNAs presented in serums derived from NPC patients appeared diverse DM risk. The miRNA sequencing was performed to identify prognostic biomarkers, and Exo-miRNAs signature was constructed using significant miRNAs obtained by LASSO regression model. The predictive model was estimated using ROC and DCA analysis. The panel of two miRNAs including miR-9-5p and miR-99a-5p exhibited robust ability for predicting DM in NPC. We subsequently established a 2-Exo-miRNAs signature in the discovery cohort, which was calculated with the results by qRT-PCR in the validation cohort. Patients were assigned to high-risk and low-risk subgroup by median value of Exo-miRNA signature, and significantly inferior DMFS was observed for those patients at high-risk ( p = 0.011). Moreover, multivariate analysis revealed that higher Exo-miRNA sig ( p = 0.036) and N2-3 stage ( p = 0.04) were independent predictors for DM in the validation set. The C-index of the incorporating model was 0.825, and the area under curve of ROC for the Exo-miRNA signature alone and incorporating model predicting 3-year DM was 0.68 and 0.91, respectively. Our study has identified a novel exosomal miRNA-based signature may serve as potential biomarkers for predicting DM in NPC.