Abstract
BACKGROUND: The current method for diagnosing endometrial cancer and monitoring treatment response is invasive and fraught with both interobserver and intraobserver variability. Less invasive and more reproducible methods are desirable. This systematic review examines the evidence for extracellular vesicles as minimally invasive biomarkers for endometrial cancer. METHODS: PubMed, Embase and Web of Science were searched for studies reporting extracellular vesicles as biomarkers in females with endometrial cancer. Risk of bias was assessed using the QUADAS-2 tool. A descriptive synthesis of biomarkers reported in the included studies was conducted. RESULTS: Of the 680 unique records reviewed, 23 studies were included. All 23 studies investigated extracellular vesicles as diagnostic biomarkers. Ten extracellular vesicle-associated biomarkers were consistently reported to be differentially abundant between endometrial cancer cases and controls in multiple independent studies and hence may be putative diagnostic biomarkers. Levels of extracellular vesicles, LGALS3BP (galectin 3 binding protein), miR-15a-5p, and miR-21-3p were elevated, while levels of miR-26a-5p, miR-130a-3p, miR-139, miR-219a-5p, miR-222-3p, and miR-885 were decreased in endometrial cancer cases versus controls. Seven studies also investigated extracellular vesicles as prognostic biomarkers, but no biomarker was reported as prognostic in more than one study. CONCLUSION: Of the ten putative diagnostic biomarkers, extracellular vesicle-associated miR-21-3p, miR-26a-5p, miR-130a-3p, miR-139 and miR-219a-5p are the most promising as their expression in extracellular vesicle preparations appears to reflect that in endometrial tissue. However, there are significant concerns regarding study quality, limited adherence to consensus recommendations on extracellular vesicle research and lack of evidence supporting biomarkers being encapsulated within extracellular vesicles.