J Cancer 2019; 10(9):1958-1967. doi:10.7150/jca.30231 This issue

Research Paper

Serum exosomal miRNA-145 and miRNA-200c as promising biomarkers for preoperative diagnosis of ovarian carcinomas

Sewha Kim1*, Min Chul Choi2*, Ju-Yeon Jeong3, Sohyun Hwang4, Sang Geun Jung2, Won Duk Joo2, Hyun Park2, Seung Hoon Song2, Chan Lee2, Tae Hoen Kim1, Hee-Jung An1✉

1. Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu Seongnam-si Gyeonggi-do 13496, Republic of Korea
2. Comprehensive Gynecologic Cancer Center, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu Seongnam-si Gyeonggi-do 13496, Republic of Korea
3. Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu Seongnam-si Gyeonggi-do 13496, Republic of Korea
4. Department of Biomedical Science, Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu Seongnam-si Gyeonggi-do 13496, Republic of Korea
*These two authors contributed equally to this article.

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Citation:
Kim S, Choi MC, Jeong JY, Hwang S, Jung SG, Joo WD, Park H, Song SH, Lee C, Kim TH, An HJ. Serum exosomal miRNA-145 and miRNA-200c as promising biomarkers for preoperative diagnosis of ovarian carcinomas. J Cancer 2019; 10(9):1958-1967. doi:10.7150/jca.30231. Available from https://www.jcancer.org/v10p1958.htm

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Abstract

Background: Exosomes are extracellular microvesicles that are released by most cells and widely distributed in various body fluids. Malignant cells secrete large amounts of exosomes containing various molecular constituents reflecting the originating tumor. We investigated the difference in microRNA (miRNA) expression in serum exosomes from the patients with benign, borderline and malignant ovarian masses to assess the diagnostic relevance of serum exosomal miRNAs as biomarkers 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, and expression levels of seven miRNAs (miRNA-21, -93, -141, -145, -200a, -200b and -200c), which were reportedly dysregulated in serous ovarian cancer in previous studies, were quantified by real-time PCR, and compared between the four groups.

Results: MiR-93, -145, and -200c, showed significantly higher expression in serum exosomes of the cancer group (HGSOC and non-HGSOC) than of the non-cancer group (benign and BOT; all p<0.05). The remaining three miRs (miR-141, -200a, and -200b) were expressed at extremely low levels, and not appropriate as serological biomarkers. To test discrimination of cancer from non-cancer, the area under the receiver operating characteristic curves determined for cancer antigen 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 showed superior sensitivity (91.6%), and miR-200c showed superior specificity (90.0%), compared with CA125.

Conclusion: Expression of exosomal miR-93, miR-145 and miR-200c was significantly elevated in the serum of ovarian cancer patients. Serum exosomal miR-145 in particular appeared to be the most promising biomarker for preoperative diagnosis of ovarian cancer.

Keywords: exosome, microRNA, ovarian cancer, serum, biomarker