Abstract 875: PAX8 protein detection in serum of patients with serous ovarian cancer

Abstract

Abstract Introduction: The paired-box (PAX) genes encode a family of transcription factors (TFs) with critical roles in the formation of tissues and organs during embryogenesis. These TFs regulate expression of gene products that control cell proliferation and differentiation. Since these processes are also essential to the development of cancer, it shows that PAX genes may participate in the initiation and proliferation of cancer. PAX8 gene expression has been demonstrated in ovarian and other malignancies of Mullerian origin and identified as a marker specific to gynecologic malignancy. Determination of tissue PAX8 protein expression by IHC is used as a clinical diagnostic tool for gynecologic cancer. However, little is known about PAX8 protein expression in serum. Identification of PAX8 in the serum of patients with ovarian cancer would be important in developing an ovarian cancer-specific biomarker. We have previously reported up-regulation of PAX8 gene in ovarian cancer using Human Focus microarrays to characterize differences in gene expression between normal and malignant tissue types. In this study, microarray (MA) and qRT-PCR were performed on human ovarian tissue from patients with normal ovaries and serous ovarian carcinoma to determine PAX8 gene expression. To determine PAX8 protein expression in serum, ELISA was used to analyze serum samples collected from patients with and without serous ovarian cancer. Methods: MA analysis of mRNA from LCM captured cells from human ovarian tissues was performed on normal and malignant ovarian tissues. These samples were analyzed using the Affymetrix Human EXON 1.0 ST microarray to distinguish the differential pattern of mRNA expression between malignant and normal samples. qRT-PCR was utilized to confirm up-regulation of PAX8 genes as determined by MA analysis. PAX8 protein on 17 normal and malignant serum samples were evaluated by indirect sandwich ELISA. RESULTS: MA analysis demonstrated up-regulation of PAX8 in serous ovarian cancer tissue in comparison with normal tissues (p=3.99E-6). This finding then was confirmed using qRT-PCR. Detection of PAX8 protein in serum was determined by ELISA and notably different between normal and malignant serum samples (p<0.03). CONCLUSIONS: This study comparing PAX8 expression in normal and serous ovarian cancer samples shows up-regulation of PAX8 in serous carcinoma of the ovary, in tissue and serum. In particular ELISA suggests that the expression patterns of PAX8 in ovarian tissues is translated to the protein component of these tissues. This resulting protein can be detectable in serum, with higher levels in malignant samples as compared to serum samples of normal human subjects. These findings warrant further study of PAX8 in additional ovarian cancers subtypes and corresponding serum, to better characterize the role of PAX8 up-regulation in ovarian cancer and validation of ELISA as diagnostic biomarker for detection of ovarian cancer. Citation Format: Zahra Bahrani-Mostafavi, Pourya Naderi Yeganeh, Megan E. Parrott, Christine Richardson, David L. Tait, M. Taghi Mostafavi. PAX8 protein detection in serum of patients with serous ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 875. doi:10.1158/1538-7445.AM2014-875