Identification of Ovarian Cancer Metastatic miRNAs (serous/omental mets)

Open access

 Abstract
Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.

 Metastases can be enriched for a distinct mutational spectrum compared to primary tumors [2], [3], [4]. Comparing primary and metastatic tumors has generated important insights into disease progression in both animal models [5] and in patients [2]. To improve treatment of metastatic disease, it is vital to understand the genes and pathways emerging in metastases that may not be present in primary tumors. Although metastatic potential can be predicted based on the primary tumor [6], [7], this observation is not mutually exclusive with the possibility that key features emerge in metastases that are not observed in primary tumors.