Objectives: Neoadjuvant chemotherapy is used in the treatment of advanced ovarian cancer. In this study, we determined the impact of chemotherapy on gene and microRNA (miRNA), expression in ovarian cancer specimens using nanofluidic technology. We performed the validation of this technique by using RNA extraction from archival formalin-fixed paraffin-embedded tissue. Molecular pathways involved in prediction of the outcome in neoadjuvant patients were analyzed. Methods: Seventy-eight patients with advanced ovarian cancer who were treated with primary surgical debulking versus neoadjuvant chemotherapy (15/78) were investigated. All patients were treated with Paclitaxel and Carboplatin. A chip 48.48 served to analyze a panel of 96 potential predictors of the outcome and response to chemotherapy. All the samples were normalized for multiple housekeeping genes and as consistent reference the ovarian cancer cell line A2780 was used. When needed for the analysis each factor was then categorized as high and low expression using the mean value as cutoff. Overall survival was analyzed using the methods of Kaplan and Meier and comparisons between groups by log-rank and Wilcoxon test. Results: We assessed the impact of neoadjuvant chemotherapy on the selected genes and microRNAs. Among the cell growth and proliferation genes MKI67, PLK1, PBK were reduced. Deactivation of the TUBB3 survival pathway, which was reduced while its negative regulator GNAI1 was increased. ERBB2 resulted downregulated in the neoadjuvant setting, while HGF and PTEN were increased. MicroRNAs expression broadly increased, with the only exception of miR-20a and miR-141. Patients exhibiting high levels of COL11A1 and PLK1 were poor performers, while the opposite occurred for GLI1. At the micro-RNA level the best predictors were miR-193a-5p, miR-375 and miR-20a. The poor performers (miR-193a-5p, miR-375) were featured by high levels of the micro-RNA while the opposite was evident for miR-20a. Conclusions: Use of the nanofluidic technology provides deeper insight into the specific roles of clinically relevant major molecular networks. Chemotherapy induced modification of genes and microRNA expression can be used as a model to develop future prognostic biomarkers and therapeutic modalities. Moreover, our findings suggest that neoadjuvant patients with ovarian cancer may benefit from biologic agent targeting HGF treatment.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3648. doi:1538-7445.AM2012-3648