Profiling studies in ovarian cancer: a review

Ovarian cancer is a heterogeneous disease with respect to histopathology, molecular biology, and clinical outcome. In advanced stages, surgery and chemotherapy result in an approximately 25% overall 5-year survival rate, pointing to a strong need to identify subgroups of patients that may benefit from targeted innovative molecular therapy. This review summarizes: (a) microarray research identifying gene-expression profiles in ovarian cancer; (b) the methodological flaws in the available microarray studies; and (c) applications of pathway analysis to define new molecular subgroups. Microarray technology now permits the analysis of expression levels of thousands of genes. So far seven studies have aimed to identify a genetic profile that can predict survival/clinical outcome and/or response to platinum-based therapy. To date, the clinical evidence of prognostic microarray studies has only reached the level of small retrospective studies, and there are other issues that may explain the nonreproducibility among the reported prognostic profiles, such as overfitting, technical platform differences, and accuracy of measurements. We consider pathway analysis a promising new strategy. The accumulation of small differential expressions within a meaningful molecular regulatory network might lead to a critical threshold level, resulting in ovarian cancer. Microarray technologies have already provided valuable expression data for classifying ovarian cancer and the first clues about which molecular changes in ovarian cancer could be exploited in new treatment strategies. Further improvements in technology as well as in study design, combined with pathway analysis, will allow us to detect even more subtle tumor expression differences among subgroups of ovarian cancer patients. Disclosure of potential conflicts of interest is found at the end of this article.