Background: Head and neck cancer (HNC) is the 6th most common cancer worldwide, with a high mortality rate1. There are currently no routine biomarkers utilized for HNC diagnosis and disease surveillance. Tumour-derived extracellular vesicles (EVs) are actively secreted tumour nanovesicles in biofluids, and have recently emerged as a potential novel biomarker, as they contain high amount of molecular content originating from the primary tumour and can represent the active clonal population2,3.
Our study aims to investigate the role of tumour-derived EVs as a novel biomarker in HNC patients undergoing therapy. We aim to: 1) Determine whether fluctuations in the amount of EV in circulation and DNA contained in tumour-derived EV correlates with treatment response; 2) Confirm if DNA tumour mutational burden is predictive of immunotherapy response and 3) Determine whether the baseline immunoprofile of EV-derived RNA reflects the tumour tissue profile and is predictive of response.
Method: Forty-one locally advanced base of tongue (n=31), and recurrent HNC (n=10) patients were consented between 2016-2018 from Sir Charles Gairdner Hospital. Serial blood samples were collected prior to and during treatment, and archived formalin fixed paraffin-embedded (FFPE) tumour samples were recalled for analysis. Tumour-derived EVs is isolated through ultracentrifugation, size exclusion chromatography and precipitation. Extracted EV-derived DNA and proteins will be correlated with clinicopathological features and patient outcome. DNA mutational profiling using targeted sequencing platform will be performed on primary tumoural DNA and tumour-derived EV DNA, and mutation burden will be correlated with response to therapy. Immune profiling of tumoural and EV-derived RNA will be performed using Nanostring technology to characterise the nature of the immune response.
The project investigates the role of EVs as a novel biomarker in HNC patients, and has the potential to change the way we diagnose and monitor disease response through routine blood tests.