Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients

摘要

Background: Owing to late diagnosis in advanced disease stages, prognosis of patients with epithelial ovarian cancer (EOC) is poor. The quantification of deregulated levels of microRNAs could facilitate earlier diagnosis and improve prognosis of EOC. Methods: Seven microRNAs (miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429) were quantified in the serum of 180 EOC patients and 66 healthy women by TaqMan PCR microRNA assays. Median follow-up time was 21 months. The effects of miR-7 and miR-429 on apoptosis, cell proliferation, migration and invasion were investigated in two (EOC) cell lines. Results: Serum levels of miR-25 ( P =0.0001) and miR-93 ( P =0.0001) were downregulated, whereas those of miR-7 ( P =0.001) and miR-429 ( P =0.0001) were upregulated in EOC patients compared with healthy women. The four microRNAs discriminated EOC patients from healthy women with a sensitivity of 93% and a specificity of 92%. The levels of miR-429 positively correlated with CA125 values ( P =0.0001) and differed between FIGO I–II and III–IV stages ( P =0.001). MiR-429 was an independent predictor of overall survival ( P =0.011). Overexpressed miR-429 in SKOV3 cells led to suppression of cell migration ( P =0.037) and invasion ( P =0.011). Increased levels of miR-7 were associated with lymph node metastases ( P =0.0001) and FIGO stages III–IV ( P =0.0001). Overexpressed miR-7 in SKOV3 cells resulted in increased cell migration ( P =0.001) and invasion ( P =0.011). Additionally, the increased levels of miR-376a correlated with FIGO stages III–IV ( P =0.02). Conclusions: Our data indicate the diagnostic potential of miR-7, miR-25, miR-93 and miR-429 in EOC and the prognostic potential of miR-429. This microRNA panel may be promising molecules to be targeted in the treatment of EOC.