Abstract A75: miR-200 family in endometriosis-associated ovarian cancer

Abstract Introduction: Epithelial ovarian cancer (EOC) is detected in late stages, when mortality is high due to the lack of an effective screening modality. One of the possible accepted precursors for endometrioid, clear cell and low grade serous ovarian tumors is endometriosis, a chronic inflammatory disease that can affect up to 10-15% of women in the reproductive age group. MicroRNAs (miRNAs) are important regulators of numerous biological pathways. In the current study, we investigated role of miRNAs in the transition from benign endometriosis to cellular atypia and to malignancies. Experimental procedure: We extracted RNA from 150 paraffin tissue blocks comprising of normal endometrium (n=31), benign endometriosis consisting of ovarian and extra ovarian endometriosis cases (n=32,) atypical endometriosis (n=15) and endometriosis associated ovarian cancer, consisting of clear cell and endometrioid ovarian cancer cases (n=41). Serous tumors (n=15) were included as non-endometriosis associated controls. Using NanoString miRNA Expression Assay, we globally profiled the expression of 800 miRNAs in these samples. Cluster analyses and differential expressions (DE) were calculated using EdgeR. We also validated our NanoString results across all disease categories by miRNA real-time PCR assays. Results: Many miRNAs are dysregulated in atypical endometriosis and cancer samples. Interestingly, several novel miRNAs have been identified that are predicted to regulate genes that may promote carcinogenesis in endometriosis, such as genes involved in estrogen signaling pathways and immune response. Among these miRNAs, differential expression of the miR-200 family between healthy controls and patients with endometriosis and EAOC is particularly intriguing. The miR-200 family of microRNAs consisting of miR-200a, 200b, 200c, 141 and 205, functions in various biological and pathological processes, especially on cellular oxidative stress response and during epithelial to mesenchymal transition (EMT). Our analysis demonstrated that expression of miR-200 family members is downregulated in endometriosis and highly upregulated in EAOC tissue as compared to normal tissues. Conclusion: Our global miRNA profiling results suggest that miR-200 family potentially plays an important role during the transition from benign endometriosis to endometriosis-associated ovarian cancer. Citation Format: Swati Suryawanshi, Anda Vlad, Robert Edwards, Raluca Budiu, Xin Huang. miR-200 family in endometriosis-associated ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A75.