Abstract
PURPOSE: Plasma extracellular vesicle (EV) miRNAs are important biomarkers for body fluid biopsy. The purpose of this study was to screen and construct a plasma small EV (sEV) miRNA panel as a biomarker for diagnosis and prognosis in laryngeal squamous cell carcinoma (LSCC). METHODS: Plasma sEV miRNAs from 6 LSCC patients with three typical anatomical sites and 3 normal controls (NCs) were analyzed by next-generation sequencing. The aberrant expression profile of sEV miRNAs was compared with the online databases of LSCC to construct and verify the diagnostic and prognostic panel by machine learning. Additionally, quantitative real-time polymerase chain reaction (qRT‒PCR) was performed to validate the diagnostic efficacy of the screened miRNAs in an independent clinical cohort. RESULTS: A plasma sEV miRNA panel (consisting of hsa-miR-139-3p, hsa-miR-486-5p, hsa-miR-944, hsa-miR-320b and hsa-miR-455-5p) was successfully constructed for the early diagnosis and prognosis of LSCC and showed good predictive potential with AUCs of 0.782, 1.000, 0.716, and 0.875 by an artificial neural network (ANN) panel in independent datasets. This panel was further validated in an independent cohort consisting of 84 clinical cases (48 LSCC and 36 NCs). In the validation cohort, the AUC of the 5 individual miRNAs ranged from 0.721 to 0.837. The accuracy was further increased by the logistic model, which further increased the AUC to 0.959 by adjusting for the number of miRNAs. The miRNA‒mRNA regulatory network and immune function analysis revealed the possible underlying pathogenesis of LSCC. CONCLUSION: Plasma sEV miRNA panels can be promising plasma biomarkers for predicting early diagnosis and prognosis in LSCC.