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

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.

SUBMITTER: Kim S

PROVIDER: S-EPMC6548168 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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

Kim Sewha S Choi Min Chul MC Jeong Ju-Yeon JY Hwang Sohyun S Jung Sang Geun SG Joo Won Duk WD Park Hyun H Song Seung Hoon SH Lee Chan C Kim Tae Hoen TH An Hee-Jung HJ

Journal of Cancer 20190512 9

<b>Background</b>: 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 preope ...[more]

PMID: 31205555

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Project description:BACKGROUND: Improved insight into the molecular characteristics of the different ovarian cancer subgroups is needed for developing a more individualized and optimized treatment regimen. The aim of this study was to a) identify differentially expressed miRNAs in high-grade serous ovarian carcinoma (HGSC), clear cell ovarian carcinoma (CCC) and ovarian surface epithelium (OSE), b) evaluate selected miRNAs for association with clinical parameters including survival and c) map miRNA-mRNA interactions. METHODS: Differences in miRNA expression between HGSC, CCC and OSE were analyzed by global miRNA expression profiling (Affymetrix GeneChip miRNA 2.0 Arrays, n = 12, 9 and 9, respectively), validated by RT-qPCR (n = 35, 19 and 9, respectively), and evaluated for associations with clinical parameters. For HGSC, differentially expressed miRNAs were linked to differentially expressed mRNAs identified previously. RESULTS: Differentially expressed miRNAs (n = 78) between HGSC, CCC and OSE were identified (FDR < 0.01%), of which 18 were validated (p < 0.01) using RT-qPCR in an extended cohort. Compared with OSE, miR-205-5p was the most overexpressed miRNA in HGSC. miR-200 family members and miR-182-5p were the most overexpressed in HGSC and CCC compared with OSE, whereas miR-383 was the most underexpressed. miR-205-5p and miR-200 members target epithelial-mesenchymal transition (EMT) regulators, apparently being important in tumor progression. miR-509-3-5p, miR-509-5p, miR-509-3p and miR-510 were among the strongest differentiators between HGSC and CCC, all being significantly overexpressed in CCC compared with HGSC. High miR-200c-3p expression was associated with poor progression-free (p = 0.031) and overall (p = 0.026) survival in HGSC patients. Interacting miRNA and mRNA targets, including those of a TP53-related pathway presented previously, were identified in HGSC. CONCLUSIONS: Several miRNAs differentially expressed between HGSC, CCC and OSE have been identified, suggesting a carcinogenetic role for these miRNAs. miR-200 family members, targeting EMT drivers, were mostly overexpressed in both subgroups, among which miR-200c-3p was associated with survival in HGSC patients. A set of miRNAs differentiates CCC from HGSC, of which miR-509-3-5p and miR-509-5p are the strongest classifiers. Several interactions between miRNAs and mRNAs in HGSC were mapped.

Dataset Information

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

Publications

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

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