Diagnostic and prognostic relevance of circulating exosomal miR-373, miR-200a, miR-200b and miR-200c in patients with epithelial ovarian cancer

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.