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(American Journal of Pathology. 2004;165:397-414.)
© 2004 American Society for Investigative Pathology

Differential Gene Expression in Ovarian Carcinoma

Identification of Potential Biomarkers

Kathleen Hibbs*, Keith M. Skubitz{dagger}, Stefan E. Pambuccian*, Rachael C. Casey*, Kathryn M. Burleson*, Theodore R. Oegema, Jr{ddagger}, Jeannine J. Thiele§, Suzanne M. Grindle, Robin L. Bliss and Amy P.N. Skubitz*

From the Departments of Laboratory Medicine and Pathology,* Medicine,{dagger} and Orthopaedic Surgery,{ddagger} College of Biological Sciences,§ and the Cancer Center, University of Minnesota, Minneapolis, Minnesota

Ovarian cancer remains the fifth leading cause of cancer death for women in the United States. In this study, the gene expression of 20 ovarian carcinomas, 17 ovarian carcinomas metastatic to the omentum, and 50 normal ovaries was determined by Gene Logic Inc. using Affymetrix GeneChip HU_95 arrays containing ~12,000 known genes. Differences in gene expression were quantified as fold changes in gene expression in ovarian carcinomas compared to normal ovaries and ovarian carcinoma metastases. Genes up-regulated in ovarian carcinoma tissue samples compared to more than 300 other normal and diseased tissue samples were identified. Seven genes were selected for further screening by immunohistochemistry to determine the presence and localization of the proteins. These seven genes were: the ß8 integrin subunit, bone morphogenetic protein-7, claudin-4, collagen type IX {alpha}2, cellular retinoic acid binding protein-1, forkhead box J1, and S100 calcium-binding protein A1. Statistical analyses showed that the ß8 integrin subunit, claudin-4, and S100A1 provided the best distinction between ovarian carcinoma and normal ovary tissues, and may serve as the best candidate tumor markers among the seven genes studied. These results suggest that further exploration into other up-regulated genes may identify novel diagnostic, therapeutic, and/or prognostic biomarkers in ovarian carcinoma.





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