Abstract
Exosomes are membrane vesicles that mediate intercellular communication by transporting their molecular cargo from cell to cell. We investigated whether serum levels of exosomal miR-373, miR-200a, miR-200b and miR-200c and circulating exosomes have diagnostic and prognostic relevance in a cohort of 163 epithelial ovarian cancer (EOC) patients using TaqMan MicroRNA assays and ELISA. The serum concentrations of exosomal miR-373 (p = 0.0001), miR-200a (p = 0.0001), miR-200b (p = 0.0001) and miR-200c (p = 0.028) were significantly higher in EOC patients than healthy women. The levels of miR-200a (p = 0.0001), miR-200b (p = 0.0001) and miR-200c (p = 0.019) could distinguish between malignant and benign ovarian tumors. While the levels of miR-373 and miR-200a were increased in all FIGO/lymph node stages (p = 0.0001), the levels of miR-200b and miR-200c were higher in patients with FIGO stage III–IV (p = 0.0001, p = 0.008, respectively) including lymph node metastasis (p = 0.0001, p = 0.004, respectively) than FIGO stages I–II. The increased levels of miR-200b and miR-200c were also associated with CA125 values (p = 0.0001, p = 0.0001, respectively) and a shorter overall survival (p = 0.007, p = 0.017, respectively). The levels of exosomes were excessively elevated in EOC patients (p = 0.0001). In all three cohorts, they were positively associated with the serum levels of exosomal miR-373 (p = 0.004), miR-200a (p = 0.0001), miR-200b (p = 0.0001) and miR-200c (p = 0.008). In conclusion, the increased levels of exosomal miR-200b and miR-200c mainly observed in advanced EOC suggest that these microRNAs may be involved in tumor progression. The high concentrations of exosomes in EOC patients imply an excessive, active exosomal secretion in EOC.
Highlights
Exosomes, small membrane vesicles in size of 30–100 nm, are actively released from multiple cell types, including dendritic cells, lymphocytes and tumor cells by exocytosis [1]
Following the quantification of exosomal miRNAs, serum of 36 epithelial ovarian cancer (EOC) patients, 20 patients with benign ovarian diseases and 32 healthy women were still available for the quantification of exosomes (Figure 1)
Apart from our study on exosomal miR-373 in the serum of breast cancer patients [23] and the study on EpCAM-specific exosomal miR-200a, miR-200b and miR-200c in the serum of EOC by Taylor and Gercel-Taylor [30] and as far as we know, our study analyzed miR-373, miR-200a, miR-200b and miR-200c in exosomes secreted into the blood serum of cancer patients for the first time
Summary
Small membrane vesicles in size of 30–100 nm, are actively released from multiple cell types, including dendritic cells, lymphocytes and tumor cells by exocytosis [1]. Computational analyses indicate that one miRNA has binding affinity to hundreds of different mRNAs and miRNAs are involved in the regulation of various cellular processes, such as development, differentiation, proliferation and tumor development [12]. In mammals, they are believed to downregulate approximately 50% of all protein-coding genes [13]. As miRNAs loci frequently map to fragile chromosomal regions harboring DNA amplifications, deletions or translocations, their expression is often deregulated during tumorigenesis, contributing to tumor progression and metastasis [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
