Extracellular Vesicle-Associated MicroRNA as a Noninvasive Diagnostic Biomarker for Epithelial Ovarian Cancer

Ovarian cancer is responsible for more deaths than any other female reproductive cancer. Only about 45% of women with ovarian cancer survive for five years past the date of diagnosis. Survival rates are greatly impacted by the type of ovarian cancer, the patient’s age, and the cancer’s stage at diagnosis. Unfortunately, most women are diagnosed with epithelial ovarian cancer (EOC) at advanced stages due to vague symptoms. EOC, the most common form of ovarian cancer, has five histopathological subtypes: high-grade serous (HGSOC), low-grade serous, clear cell, endometrioid, and mucinous. There remains great interest in developing minimally invasive approaches to detect EOC using novel circulating biomarkers found in bodily fluids. Extracellular vesicles (EVs) are produced by nearly all cells and are abundant in human biofluids. EVs encapsulate and protect biomarkers, such as, microRNA (miRNA), which are small non-coding RNA molecules capable of broadly regulating the expression of hundreds of proteins. We compared three EV isolation approaches, i.e., tetraspanin capture, membrane-based affinity, and ITGA5/ITGB3 immunocapture and found that as we enrich for disease relevant EVs, that that EV-microRNA signatures become more informative. Although EV-miRNA patterns reliably distinguish EOC patients from individuals with no reported cancer using blood plasma, the integrin capture method was superior when focused on the HGSOC subtype. This study demonstrated that specific subpopulations of EVs possess disease-specific miRNA signatures that can be exploited to diagnose EOC at an earlier stage, when survival is optimal.