Extracellular Vesicle Proteomic Fingerprinting of Ovarian Cancer for Early Detection with a Nanoengineered Microsystem

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Project Summary/Abstract Diversity Supplement Title: Identification of Plasma Microbiota Biosignatures for Early Epithelial Ovarian Cancer Detection Annually over 21,000 women are diagnosed in the United States with ovarian cancer and nearly 14,000 women die of the disease. Advanced epithelial ovarian cancer (EOC) is associated with an overall survival of 30% but can be cured in up to 90% of cases if diagnosed at an early stage. Therefore, developing noninvasive and highly specific blood-based tests is highly appealing as screening methods in clinic settings. Research suggests that human microbiota, a collection of microorganisms that live in the body, are harbored in EOC tumor tissue that are distinctly unique between women with and without disease. However, additional research is needed to determine if these observed microbiota differences can be detected outside the ovarian tumor microenvironment and serve as biomarkers of early disease. Recent investigations have identified noninfectious microbial deoxyribonucleic acid (DNA) isolated in blood plasma from individuals with other cancers, which creates an exciting opportunity for ovarian cancer screening innovation. The purpose of this diversity supplement proposal is to identify and validate plasma microbial biosignatures detected in EOC that can drive the development of non-invasive blood tests for early disease screening. This study applies a retrospective design that will use existing consortium biobank plasma specimens including EOC cases, non-EOC solid tumor cases, benign gynecologic disease cases, and control cases. We will evaluate the microbial signatures of plasma samples with 16S rRNA gene sequencing and assess the clinical sensitivity and specificity of the most informative microbial taxa signature that rigorously discriminates between cases with and without EOC. This proposal marks a dynamic change in thinking to postulate that EOC-favorable microbiota may coalesce in the bloodstream early and signify ovarian carcinogenesis. We believe this innovative study will allow us to develop a method to detect early EOC during a routine well women exam by screening blood samples for unique bacterial DNA signatures, especially in women who are at high risk.