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

Cancers (Basel). 2024 Nov 11;16(22):3793. doi: 10.3390/cancers16223793.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: HPV; biomarkers; extracellular vesicles; head and neck squamous cell carcinoma (HNSCC); liquid biopsy; microRNA; oncology; oropharyngeal carcinoma.