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Extracellular vesicle micro RNA cargo is correlated with HPV status in oropharyngeal carcinoma
Author(s) -
Peacock Ben,
Rigby Alice,
Bradford James,
Pink Ryan,
Hunter Keith,
Lambert Daniel,
Hunt Stuart
Publication year - 2018
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12781
Subject(s) - rna , cell , extracellular vesicle , cancer research , extracellular , carcinoma , biology , cell culture , microrna , chemistry , gene , microvesicles , microbiology and biotechnology , genetics
Background The incidence of human papilloma virus positive ( HPV + ) oropharyngeal squamous cell carcinoma ( OPSCC ) has increased rapidly in recent decades. These tumours have a favourable outcome compared to HPV ‐negative ( HPV − ) OPSCC . However, HPV + tumours are more likely to metastasise to distant sites, suggesting a difference in how these tumour subtypes interact with the metastatic niche. Extracellular vesicles ( EV s) have emerged as important players in cell‐to‐cell communication and are a potential source of biomarkers for cancer diagnosis. This study aims to characterise the micro RNA cargo of small EV s released by HPV + and HPV − OPSCC cell lines. Methods Extracellular vesicles produced by HPV + ( SCC 2 and SCC 90) and HPV − ( SCC 72 an SCC 89) OPSCC cells were characterised by tunable resistive pulse sensing ( TRPS ) and western blotting. RNA was extracted from EV s and analysed by small RNA sequencing. A bioinformatics approach was used to identify EV mi RNA signatures associated with HPV status. Results HPV − OPSCC cells produced more EV s than HPV + OPSCC cells. EV s were positive for the common EV markers CD 63, CD 9 and TSG 101. Unbiased hierarchical clustering analysis of EV mi RNA cargo revealed that samples clustered based on HPV status. 14 mi RNA were enriched in HPV + cell‐derived EV s, whereas 19 mi RNA were enriched in EV s derived from HPV − cell lines. Conclusions Here, we identify EV mi RNA signatures indicative of the HPV status of the parent cell. This may provide a platform from which to validate salivary or blood‐based biomarkers with utility for early detection and stratifying risk in OPSCC patients.