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Abstract
Abstract Objectives: To identify the key microRNAs (miRNAs) and their top co-targets in patients of elderly ovarian papillary serous carcinoma (OPSC) patients with advanced stage and ovarian clear cell carcinoma (OCC), for the insight of possible regulation gene and pathway of epithelial ovarian cancer (EOC) prognosis. Methods: The study was opened to patients with primary, previously untreated EOC referred to member institutions. Pathologic diagnosis was confirmed by central review. High-throughput analysis of the miRNA profile in a panel of OCC and OPSC cells was assessed using a microarray platform. The miRNA-targets and possible pathway were predicted by TargetScans, MicroCosm Targets version 5, miRBase and Ingenuity. Finally, the downstream predicated co-target, activating transcription factor 3 (ATF3) was validated by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and immunohistochemical (IHC) assay. Results: Of the 667 miRNAs analyzed from human, we identified 83 as enriched in the OPSC, and 15 in OCC (P<0.01 for all). Seventeen of 667 miRNAs were significantly expressed with at least 3 fold differences in the OPSC versus OCC. The expression of tree miRNAs (miR-30a*, miR-30e*, miR-505*) were most significantly lower in OCC comparing to elderly OPSC patients with advanced stage. ATF3, the top co-target gene of three key miRNAs mentioned above was highly expressed in OCC lesions, and a stronger distribution was shown in protein level of ATF3 by immunohistochemistry in OCC than OPSC lesions. Conclusions: We identified the key miRNAs that differentially expressed in patients of elderly OPSC with advanced stage and OCC tumors, predicted and validated the most popular co-target shared by the key miRNAs, indicating the possible regulation gene and pathway for EOC prognosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4615. doi:1538-7445.AM2012-4615
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