Abstract 4188: Association of HOX gene expression with osteopontin in ovarian cancer: Implications for biomarker development

Abstract Ovarian cancer is characterized by poor early detection and serves as an excellent model system to develop potential markers for early diagnosis. Osteopontin is a glycophosphoprotein known to demonstrate multiple functions including mediation of cellular adhesion, suppression of macrophage interleukin production, prevention of angiogenesis, apoptosis, and inhibition of anchorage-dependent growth. Studies of Osteopontin in ovarian cancer have described increased expression and a role as a candidate biomarker. Secretion of Osteopontin into the extra cellular matrix is reported to facilitate metastasis and has been reported to be inhibited by the presence of cytoplasmic Homeobox proteins (HOX). The HOX family of genes encodes transcription factors involved in basic developmental processes and has been linked to oncogenesis. Dysregulation of HOX genes may be an early event in malignant transformation making the HOX gene family appealing for biomarker investigation. In this study we characterize HOX gene expression in malignant tumors of the ovary compared to Osteopontin, a known biomarker for ovarian cancer. Methods: Microarray analysis of mRNA from human ovarian tissues was performed on samples of normal, benign, and malignant ovarian tissues. These samples were analyzed using the Affymetrix Human Genome Focus GeneChip (HG-Focus) microarray to distinguish the differential pattern of mRNA expression between the three types of samples. Immunohistochemistry staining of ovarian tissue samples was utilized to analyze confirmatory protein expression of the microarray findings. Results: Microarray analysis demonstrated up-regulation of HOXB2, HOXB7, and Osteopontin genes in malignant ovarian tumor samples compared to normal ovarian tissue controls. Conversely, HOXC6 was down-regulated in malignant tissue samples. Immunohistochemistry was performed for HOXB2, HOXC6 and Osteopontin on OCT embedded tissues samples. Similarly, increased protein expression was shown for HOXB2 and Osteopontin in malignant samples and increased HOXC6 in non-cancerous samples. Conclusion: Our results demonstrate multiple HOX genes to be up-regulated in ovarian cancer. Increased expression of HOXB2 and HOXB7, correlated with increased Osteopontin expression found in malignant ovarian tissue samples. HOXC6 demonstrated an inverse relationship with Osteopontin in non-cancerous ovarian tissue samples. The association of these HOX genes with Osteopontin expression warrants further investigation into the role of HOX genes as candidate biomarkers for ovarian cancer. 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 4188. doi:10.1158/1538-7445.AM2011-4188