Introduction: MicroRNAs (miRNAs) are non-protein-coding, endogenous, small RNAs that can bind complementary mRNA to modulate gene expression and protein translation. Recent studies indicate that miRNAs may be mechanistically involved in the development of various human cancers, suggesting that they represent a promising new class of cancer biomarker. The objective of the current study was to explore the role of miRNAs in ovarian cancer development and response to therapy.

Material and Methods: MicroRNA was extracted from 63 samples including 16 ovarian cancer cell lines and 5 immortalized normal ovarian surface epithelial (NOSE) samples in triplicate, and 20 advanced stage serous epithelial ovarian cancers resected from patients who went on to receive platinum-based primary chemotherapy. Ten of these patients demonstrated a complete- [CR] and 10 an incomplete-response [IR] to primary therapy. All samples were hybridized to a microRNA array that contained Ambion and Invitrogen probe sets. Bayesian and logistic regression analyses were used to identify miRNAs associated with ovarian cancer and platinum sensitivity. MiRNA expression levels were validated by quantitative real-time polymerase chain reaction (qRT-PCR).

Results: Bayesian regression analysis identified 4 miRNAs (miR-125b, miR-379, miR-127, and miR-100) that discriminate between ovarian cancer cell lines and NOSE samples, and 13 miRNAs that discriminate between CR and IR ovarian cancer samples. This 13-miRNA profile correctly classified 17/20 (85%) samples as CR versus IR in leave-one-out cross validation. Linear regression analysis identified 2/13 platinum-predictive miRNAs (miR-185 and miR-339) to be associated with in-vitro cell line platinum responsiveness also (p<0.04). Conclusion: We have identified miRNAs that may influence ovarian cancer development and response to chemotherapy. Our data suggest that miRNA profiles may not only aid in discriminating between platinum sensitive and resistant ovarian cancers, but may also represent novel therapeutic targets for patients with chemo-resistant disease.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA