Abstract 1999: Aberrant expression of HOX transcript in ovarian carcinoma

Abstract Ovarian cancer is a complex disease phenotype that is challenging to diagnose, primarily because patients tend to remain non-symptomatic until after metastasis has initiated. For those individuals identified early in the disease progression the survival rate is promising, but for the majority, diagnosed late, the 5-year survival rate is dismal. Our eventual goal is to identify a panel of circulating markers that distinguish early onset of the disease. In particular, we have examined the homeobox (HOX) transcript family of genes, known to be involved in cancer progression. These genes are intrinsic cellular factors regulating positional development during embryogenesis and bone formation, and are documented upstream regulators of 16 signaling pathways. Methods: The tissue-specific gene expression from 35 human ovarian tissue samples, using Affymetrix GeneFocusTM microarrays was examined. The microarray analysis was performed on tissues from 8 normal ovaries, 12 benign and 15 malignant epithelial tumors. Microarray output was processed with a stringent data cleansing pipeline to ensure the investigated genes can be unambiguously interpreted. Results: ANOVA analysis reveals a significant alteration in the HOX expression profiles between ovarian tumorous and non-tumorous tissues. While several members of the homeobox gene family are reported to be differentially expressed, we observed a significant shift from healthy HOXC6 expression to an aberrant HOXB2 expression. Whereas non-tumorous tissue demonstrated elevated levels of HOXC6 mRNA transcript, the malignant tissues demonstrated elevated levels of HOXB2 transcript. A possible consequence of the aberrant HOX expression levels is to increase the production and hence the paracrine signaling of osteopontin (SPP1), which is reported to be negatively regulated by a SMAD-HOX interaction. Osteopontin has been correlated to cancer progression, metastasis, and patient survival. We observed a significant correlation between elevated SPP1 expression and the observed HOX disregulation. Conclusion: We demonstrated a correlation between malignant associated SPP1 upregulation and aberrant HOX transcript regulation. These alterations in transcript and protein levels are significant to the epithelial microenvironment. These results have been validated by qRT-PCR and IHC and confirmed with additional patient specimens. The correlation between these two events needs to be further investigated as to their significance in the progression of the disease and as potential candidate biomarkers for ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1999.