Abstract
Abstract Current diagnostic methods for ovarian cancer include gynecological inspection, ultrasound-imaging and detection of the serum tumor marker CA-125. Even combined, these methods are insufficient in specificity and sensitivity for detection of early disease. Since the majority of ovarian carcinomas are of epithelial origin, the carcinogenesis has thought to be induced in the epithelial layer of the ovaries or fallopian tubes. However, recent findings indicate that many ovarian cancers originate from non-ovarian tissues and therefore different ovarian cancer histotypes should be regarded as distinct diseases. Currently the histotype of ovarian carcinomas can be determined only during surgery. There is an increasing need for more sensitive and specific biomarkers for ovarian cancer diagnosis as well as for prediction of biological tumor behavior. In this study, genes with ovarian cancer specific expression profile were identified from publicly available gene-expression databases. In order to find potential serum biomarker candidates, further in silico data mining was performed utilizing the GeneSapiens database. The identified ovarian cancer specific and potentially secreted or surface-expressed genes were validated in vitro in patient samples and primary ovarian cancer cells lines with qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The presence of the candidate biomarkers in patient serum samples was studied with dot blotting and immunoprecipitation. Finally, the expression levels of the candidate genes were compared to the pre-operative CA-125 and HE-4 levels in a cohort of prospective collected advanced ovarian cancer patients. The in silico data analyses resulted in identification of altogether six novel serum biomarker candidates for serous, mucinous and clear cell ovarian tumors. Analysis of tumor samples and primary cell lines derived from ovarian cancer patient samples confirmed the expression of the candidate genes in ovarian carcinomas. Furthermore, the mRNA analysis showed evidence of histotype specificity, especially in the case of potential biomarkers for mucinous ovarian carcinoma. Immunohistochemical staining of several tumor tissue samples showed distinctive cytoplasmic expression pattern characteristic for secreted proteins. Further analysis of the presence of the biomarkers in the sera of the patients and matched controls is in progress. Citation Format: Laura Lehtinen, Kristiina Iljin, Johanna Hynninen, Annika Auranen, Caj Haglund, Seija Grenman, Olli Carpén. Novel serum biomarkers for histotype specific ovarian cancer diagnosis. [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 A2.
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