Gene Expression Profiling of Epithelial Ovarian Cancer

Anette      Sommer; Felix      Hilpert; Norbert      Arnold

Abstract

Gene expression profiling using microarrays and SAGE is a widely used technology to elucidate important aspects of epithelial ovarian cancer (EOC) in order to improve the clinical management of this disease: Despite the high degree of morphological heterogeneity, epithelial ovarian cancer gene expression profiling reflects morphology and biological behaviour. Based on multiple studies, gene expression profiling results can be used to stratify the four different subtypes of EOC, namely serous papillary, mucinous, endometrioid, and clear cell carcinoma, but some overlapping gene expression was also noted. An aneuploid DNA content is a frequent phenomenon in EOC as well as in other solid tumours. However, when differential RNA expression and the DNA copy number as measured by comparative genomic hybridisation (CGH) were compared, the level of concordance was not significant in most studies. The reason for this will mostly lie in the low resolving power of currently used CGH methods and might improve with a wider access to arrayCGH. Several novel candidate markers for the early detection of EOC have been identified by gene expression profiling and examples that have been validated by ELISA on the protein level in serum from EOC patients and healthy controls are discussed. The information from gene expression profiling experiments is now being overlaid with additional information from Gene Ontology, protein-protein interaction and signal transduction pathway databases in order to discover novel therapeutic pathways and targets. Genes involved in cell cycle regulation, the extracellular matrix, and in immunological responses are relevant to epithelial ovarian cancer biology and particular genes might have the potential to be exploited as therapeutic targets for small molecules, biologicals, and immunologicals. We hope to accomplish that the scope of the review which includes a discussion of the recently published papers and the implications of the results for the clinical management of EOC is of help to researchers and clinicians in the field.

Keywords: Epithelial ovarian cancer, tumour of low malignant potential, ascites, comparative genomic hybridisation, gene expression profiling, microarray, signal transduction pathway, diagnostic marker, therapeutic target