Exosomal miRNA and mRNA signatures as liquid biomarker for head and neck cancer

Introduction Exosomes are small extracellular vesicles that mediate intercellular communication. HNSCC patient’s plasma is enriched in immunomodulatory exosomes which correlate with clinical parameters. In this study we compare for the first time miRNA and mRNA signatures of plasma-derived exosomes and corresponding tumor cells in order to evaluate their potential biomarkers for HNSCC.

Methods Exosomes were isolated from plasma of 16 HNSCC patients and 12 healthy donors (HD). Primary tumor cells were obtained from the same HNSCC patients. Total exosomal and tumor RNA was used for targeted RNA profiling. Differential presence and discriminatory potential of exosomal RNAs between HNSCC and HD were analyzed.

Results Of all detected exosomal RNAs, 55% miRNAs and 31% mRNAs were HNSCC-exclusive, while 8% miRNAs and 48% mRNAs were HD-exclusive. 91 miRNAs and 347 mRNAs were significantly differentially present between HNSCC and HD exosomes. Both exosomal RNA signatures could successfully assign samples to “Tumor” or “Healthy”. 165 miRNAs and 146 mRNAs overlapped between corresponding tumor and exosomes and were considered as tumor-originating RNAs. These were filtered to 23 miRNAs inversely targeting 17 mRNAs, e.g. upregulated miR-421-3p targeting downregulated, anti-tumor IL15. Identified core hubs of tumor-originating RNAs were related to TLR, NF-κB and IFN signaling.

Conclusions Exosomal miRNA and mRNA signatures have high discriminatory potential between HNSCC patients and HD. Final RNA candidates are currently validated in an independent cohort. Identified RNAs were related to pathways of immune regulation, inflammatory response and cellular development which highlights their relevance for disease pathogenesis.

DFG

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Artikel online veröffentlicht:
12. Mai 2023