Extracellular Vesicle microRNAs as Possible Liquid Biopsy Markers in HNSCC-A Longitudinal, Monocentric Study.

Abstract

Biomarkers for HNSCC are still lacking. Biomolecules obtained via liquid biopsy are being investigated for diagnosis, prognosis, and therapy monitoring, including extracellular vesicles (EVs) and EV-cargo, e.g., proteins, RNA, and microRNA. This study aims to understand localization-dependent EV-microRNA expression in blood sera, their dynamics over time (12 months FU), and insights into their potential in diagnostics and therapy monitoring. Via liquid biopsy, blood serum was taken from 50 patients with HNSCC and 16 controls. Extracellular vesicles were isolated from serum by precipitation, and the contained microRNA-21, -1246, -200c, -let-7a, -181a, and -26a were amplified by reverse transcription and determined with real-time PCR. Expression ratios (HNSCC to healthy controls) were collated with the patients' clinical parameters. A second liquid biopsy was carried out avg. 12 months later in the tumor aftercare. A sub-analysis with the Oropharynx subsite was implemented. EV-mir-21, -let-7a, and -181a were 2.5-3-fold higher expressed in HPV/p16+ than in HPV/p16- HNSCC. Different expressions of EV-mir-181a and -26a could be demonstrated depending on the therapy modality. EV-microRNA could be a promising biomarker in the diagnosis and therapy monitoring of HNSCC. A systematic comparison of EV- and tissue microRNA expression in different HNSCC-subsites is needed.