miR-187-5p and miR-219a-1-3p: potential biomarkers associated with chemotherapeutic response and prognosis in ovarian cancer

Background: Epithelial ovarian cancer (EOC) is the fifth-most common cause of female cancer death and is associated with high recurrence and mortality despite recent advancements in therapeutic strategies. Chemoresistance remains the main cause of treatment failure in EOC patients. The aim of this study is to identify specific miRNA markers closely associated with the chemoresponse in EOC patients.

Methods: We analyzed 374 serous ovarian cancer patients who receiving combination chemotherapy from The Cancer Genome Atlas (TCGA) and identified the most significantly altered miRNAs between different groups patients of chemotherapy response. We then used Kaplan-Meier and log-rank methods to analyze the relationship between these miRNAs and progression-free and overall survival in TCGA (n = 460) and Bagnoli (n = 130) datasets. In vitro study for response to chemotherapy agents were performed in human ovarian cancer cell lines and their transfectants. The biological relevance of putative miRNA targets was also analyzed using bioinformatics.

Results: MiR-187-5p and miR-219a-1-3p were associated with better response to chemotherapy and longer progression-free and overall survival in two independent epithelial ovarian cancer patient cohorts (all p <0.05). These two miRNAs also sensitized ovarian cancer cells to chemotherapy, thus recapitulating the clinical observation.

Conclusions: This study showed that miR-187-5p and miR-219a-1-3p could be useful biomarker for prediction of chemotherapy response and survival in serous ovarian cancers. MiR-187-5p and miR-219a-1-3p may be potential molecules in the treatment of EOC for sensitizing cancer cells to chemotherapy.