Development of lavage EV protein biomarkers for minimally-invasive detection of endometrial cancer

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PROJECT SUMMARY Early detection of endometrial cancer can increase the 5-year survival rate from <20% to >95%. However, currently there are no non-invasive methods for its detection. We propose the use of cell-secreted extracellular vesicles (EVs) as the source of new diagnostic biomarkers from uterine lavage – a sample that is much more targeted to endometrial cancer. Within the scope of biomarker detection, EVs offer numerous benefits for clinical analysis, including non-invasive collection, a suitable sample source for longitudinal disease monitoring, higher stability and sample volumes, faster processing times and lower cost. However, the analysis of exosomes and other EV has not really been possible for early endometrial cancer detection. The common procedures for biofluid EV biomarker analysis are very long and cumbersome due to extremely low target levels and high background of free proteins. In order to enable better biomarker discovery and endometrial cancer diagnosis, a more reliable and efficient approach is needed, capable of enriching potential cancer-associated proteins with higher purity. In this NIH SBIR Phase I study, we will implement our novel method for fast and reproducible enrichment of EVs with >95% recovery yield and >99.9% purity for analysis of endometrial cancer from lavage samples. We have already carried out initial lavage EV validation and biomarker discovery experiments, and selected over a dozen of high-quality protein targets that enable effective differentiation of endometrial cancer from non-cancer controls. The following aims will be completed in the Phase I of the proposal: Aim #1: Determine the feasibility of the discovered endometrial cancer biomarkers from lavage EVs to differentiate the disease and refine the panel. Aim #2: Evaluate and implement the novel uterine lavage collection device for fast and effective EV isolation and measurement. By the completion of this project, the non-invasive endometrial cancer biomarker discovery platform from lavage EVs will be developed, and a minimally invasive early endometrial cancer detection assay will be validated that can overcome the limitations of current approaches, and thus could have an enormous public health impact and market potential.