Clinical Impact of microRNAs Associated With Cancer Stem Cells as a Prognostic Factor in Ovarian Carcinoma.

Ovarian carcinoma is a highly lethal gynecological malignancy due to its frequent relapses and adoption of chemoresistance. To develop new biomarkers for disease progression in ovarian carcinoma, CSCs, which are considered to contribute to disease relapse and metastasis, were isolated from human ovarian carcinoma tissues, and differentially expressed microRNAs (miRNAs) in CSCs were identified and assessed the clinical implication of expression of these miRNAs. Primary cancer cells derived from human ovarian carcinomas were cultured and spheroid-forming cells (SFCs) were isolated. Profiles of miRNA expression in CSC-like SFCs were identified by miRNA microarray and the results were validated by quantitative real-time RT-PCR (qRT-PCR). We also assessed the correlations between miRNA expression levels and clinicopathological parameters in ovarian carcinomas. Five miRNAs (miR-5703, miR-630, miR-1246, miR-424-5p, and miR-320b) were significantly dysregulated in CSC-like SFCs compared with primary cancer cells. The qRT-PCR showed that miR-5703 and miR-1246 expression was significantly higher in ovarian cancer cells than in normal control cells, whereas the miR-424-5p level was significantly lower. Decreased expression of miR-424-5p was significantly associated with distant metastasis in high stage (stage IIII & IV) carcinomas (35.5% vs. 72.2%, respectively, p=0.013) Taken together, miR-5703, miR-630, miR-1246, miR-424-5p, and miR-320b are useful markers for enriching ovarian CSCs. Decreased expression of miR-424-5p in ovarian carcinoma might be a putative biomarker for distant metastasis in ovarian carcinoma.