Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma

Abstract

Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC.