title: 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.
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Müller
authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Milde-Langosch
authors.affiliation: Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Trillsch
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Schwarzenbach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D012372:ROC Curve; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C533896:MIRN200 microRNA, human; C527114:MIRN373 microRNA, human; D035683:MicroRNAs
keywords: diagnosis; epithelial ovarian cancer; exosomal miRNAs; exosomes; prognosis