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Journal of cancer, 2019. 10(9), 1958-1967, DOI: https://doi.org/10.7150/jca.30231
Serum exosomal miRNA-145 and miRNA-200c as promising biomarkers for preoperative diagnosis of ovarian carcinomas
Sewha Kim, Min Chul Choi;Ju-Yeon Jeong;Sohyun Hwang;Sang Geun Jung;Won Duk Joo;Hyun Park;Seung Hoon Song;Chan Lee;Tae Hoen Kim;Hee-Jung An
Background: Exosomes are extracellular microvesicles that are released by most cells and widelydistributed in various body fluids. Malignant cells secrete large amounts of exosomes containingvarious molecular constituents reflecting the originating tumor. We investigated the difference inmicroRNA (miRNA) expression in serum exosomes from the patients with benign, borderline andmalignant ovarian masses to assess the diagnostic relevance of serum exosomal miRNAs asbiomarkers for preoperative diagnosis of ovarian carcinoma.
Methods: A total of 68 cases of ovarian masses were enrolled, comprising benign ovarian cysts(benign; n=10), borderline ovarian tumors (BOT, n=10), high-grade serous ovarian carcinomas(HGSOC, n=39) and non-HGSOCs (n=9). Exosomal RNA was extracted from the serum, andexpression levels of seven miRNAs (miRNA-21, -93, -141, -145, -200a, -200b and -200c), whichwere reportedly dysregulated in serous ovarian cancer in previous studies, were quantified byreal-time PCR, and compared between the four groups.
Results: MiR-93, -145, and -200c, showed significantly higher expression in serum exosomes of thecancer group (HGSOC and non-HGSOC) than of the non-cancer group (benign and BOT; allp<0.05). The remaining three miRs (miR-141, -200a, and -200b) were expressed at extremely lowlevels, and not appropriate as serological biomarkers. To test discrimination of cancer fromnon-cancer, the area under the receiver operating characteristic curves determined for cancerantigen 125 (CA125), miR-145, miR-200c, miR-21, and miR-93 were 0.801 (p<0.001), 0.910(p<0.001), 0.802 (p<0.001), 0.585 (p=0.303), and 0.755 (p=0.002), respectively. MiR-145 showedsuperior sensitivity (91.6%), and miR-200c showed superior specificity (90.0%), compared withCA125.
Conclusion: Expression of exosomal miR-93, miR-145 and miR-200c was significantly elevated inthe serum of ovarian cancer patients. Serum exosomal miR-145 in particular appeared to be themost promising biomarker for preoperative diagnosis of ovarian cancer.
- DOI: https://doi.org/10.7150/jca.30231
- ISBN or ISSN: 1837-9664
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- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.