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. 2019 May 12;10(9):1958-1967.
doi: 10.7150/jca.30231. eCollection 2019.

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

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

Sewha Kim et al. J Cancer. .

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: biomarker; exosome; microRNA; ovarian cancer; serum.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Expression levels of serum exosomal miR-145, 200c, 21, and 93 determined by qRT-PCR in patients with benign ovarian cyst (benign), borderline ovarian tumor (BOT), high-grade serous ovarian carcinoma (HGSOC), and non-HGSOC. The expression levels of miR-145 and miR-200c were significantly different between the HGSOC and non-cancer (benign or BOT) groups. By contrast, significant differences in miR-21 and miR-93, were found between non-HGSOC and non-cancer groups. The horizontal lines indicate median values.
Figure 2
Figure 2
Difference in expression of serum exosomal miRs between non-cancer (benign/BOT) and cancer (HGSOC/non-HGSOC) groups. Expression levels of miR-145, -200c, and -93 were significantly increased in the cancer group compared with the non-cancer group. Data represent mean ± standard error on the mean (SEM). Benign, benign ovarian cyst; BOT, borderline ovarian tumor; HGSOC, high-grade serous ovarian carcinoma.
Figure 3
Figure 3
Receiver operating characteristic (ROC) curve analysis for the prediction of carcinoma by CA125, serum exosomal miR-145, -200c, -21, and -93. AUC, area under the ROC curve; CI, confidence interval.

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