Abstract

Abstract Serous epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy; due in part to vague and non-specific symptoms resulting in delayed diagnosis. The biomarker in routine clinical use for EOC is CA-125, with the OVA1 test (Quest Diagnostics) recently available to aid in predicting the likelihood that an ovarian mass is malignant. Current diagnostic tests have limitations which may be improved by expansion of biomarker panels. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate important cellular processes. They exhibit distinct expression profiles in cancers and have recently been discovered in serum and other body fluids. Tumor miRNAs may be shed into the circulation, raising the possibility of their use as serum biomarkers for the detection of EOC. Exiqon LNA miRNA microarrays were performed using RNA from cell line models of serous EOC. Over-expressed miRNAs were selected as candidates for assessment in serum. These were measured in RNA extracted from serum of patients with serous EOC (n=30) and healthy age-matched volunteers (n=30) by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). As there are currently no routine methods for the normalization of miRNA in serum, a group of highly and uniformly expressed miRNAs with no reported involvement in cancer was selected for assessment as endogenous controls. Five miRNAs, miR-182, miR-96 and miR-200a, miR-200b and miR-200c were identified as highly expressed in a panel of serous EOC cell lines consistent with previous reports, and therefore selected for investigation as putative serous EOC biomarkers. In addition, miR-92a, miR-103, miR-638 and RNU48 were selected as candidate endogenous controls given that they were consistently expressed at high levels in the cell line panel. qRT-PCR data will be presented on the expression of these 8 candidate miRNAs and RNU48 either with or without pre-amplification of target sequence. In conclusion, miR-92a, miR-103 and miR-638 were observed to show little variation between patients and healthy volunteer serum. These results identify the potential for these miRNAs to be used as endogenous controls for the expression of miRNA in serum. Reliable detection of specific miRNAs in serum from women with serous EOC may improve the detection of this malignancy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4962. doi:10.1158/1538-7445.AM2011-4962

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