Abstract
Endometrial cancer (EC) is the sixth most common cancer in women worldwide and is responsible for more than 89,000 deaths every year. Mortality is associated with presence of poor prognostic factors at diagnosis, i.e., diagnosis at an advanced stage, with a high grade and/or an aggressive histology. Development of novel approaches that would permit us to improve the clinical management of EC patients is an unmet need. In this study, we investigate a novel approach to identify highly sensitive and specific biomarkers of EC using extracellular vesicles (EVs) isolated from the peritoneal lavage of EC patients. EVs of peritoneal lavages of 25 EC patients were isolated and their miRNA content was compared with miRNAs of EVs isolated from the ascitic fluid of 25 control patients. Expression of the EV-associated miRNAs was measured using the Taqman OpenArray technology that allowed us to detect 371 miRNAs. The analysis showed that 114 miRNAs were significantly dysregulated in EC patients, among which eight miRNAs, miRNA-383-5p, miRNA-10b-5p, miRNA-34c-3p, miRNA-449b-5p, miRNA-34c-5p, miRNA-200b-3p, miRNA-2110, and miRNA-34b-3p, demonstrated a classification performance at area under the receiver operating characteristic curve (AUC) values above 0.9. This finding opens an avenue for the use of EV-associated miRNAs of peritoneal lavages as an untapped source of biomarkers for EC.
Highlights
Endometrial cancer (EC) is the sixth most common cancer in women worldwide and is responsible for more than 89,000 deaths every year [1]
extracellular vesicles (EVs) have attracted the interest of the scientific community as a source of biomarkers, mainly because they carry a broad range of bioactive material that is well-protected by the lipid bilayer membrane of EVs, even if they are extracted from circulating or proximal bodily fluids or frozen before any experimental study [10]
We investigated for the first time the miRNA content of EVs isolated from peritoneal lavages and ascitic fluids of EC and control patients, respectively
Summary
Endometrial cancer (EC) is the sixth most common cancer in women worldwide and is responsible for more than 89,000 deaths every year [1]. EVs have attracted the interest of the scientific community as a source of biomarkers, mainly because they carry a broad range of bioactive material (proteins, metabolites, RNA, miRNA, etc.) that is well-protected by the lipid bilayer membrane of EVs, even if they are extracted from circulating or proximal bodily fluids or frozen before any experimental study [10]. We investigate the use of EVs isolated from the peritoneal lavage, a proximal fluid of EC, as a source potential. Ofwe investigate use of EVs isolated fromlavage, the peritoneal lavage, proximal fluidthe of manipulation uterus, used forThe staging purposes according to just the before old International. The study was conceived as a relevant individual miRNAsand related to EC and characterized the biological and molecular landscape proof concept to demonstrate thea feasibility of usinginvestigation the peritonealtolavage as a source of theof milieu.investigation. Feasibility of using the peritoneal lavage as a source of EV-associated miRNA biomarkers of EC
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