Abstract 4930: An integrated proteomic and bioinformatic approach identifies a subset of EGFR-expressing epithelial ovarian cancer
Authors: Pinciroli Patrizia , Alberti Chiara , Sensi Marialuisa , Ferri Renata , Valeri Barbara , Canevari Silvana , Tomassetti Antonella 
Published: June 2012

Epithelial Ovarian Cancer (EOC) is initially characterized by intraperitoneal growth of tumor masses followed by an accumulation of ascitic fluid containing tumor cells, inflammatory leukocytes, cytokines and chemokines. Among those latter, IL-6 and IL-8 have been found to contribute to cell proliferation of EOC. EGFR, detected in up to 60% of EOCs, is associated with poor outcome. EGFR overexpression has been also associated to chemotherapy resistance. However, treatment of EOC patients with anti-EGFR resulted to give very poor response. In this study we show that EGF stimulation of EOC lines IGROV1 and OAW42, displaying comparable high expression levels of EGFR, induced, in conditioned medium of both cell lines production of several cyto/chemokines as detected by Bioplex analysis. IL-6, PAI-1 and IL-8 were however specifically produced upon EGFR activation only in IGROV1 and, conversely, silencing of EGFR in this cell line abrogated, following stimulation, their induction. Immunohistochemistry of EOC tissue samples with an anti-P(Y1173)-EGFR and dosage of IL-6 in the corresponding ascitic fluids indicated that, although not significant, IL-6 levels trended upwards with P-EGFR expression. Moreover in the ascitic fluids from EOC patients IL-6 and PAI-1 significantly correlated (Spearman correlation: r=0.79). In order to elucidate the molecular determinants of EGFR-, IL-6-, PAI-1- and IL-8-expressing EOC, a computational analysis was performed on the gene expression profile of 204 serous EOC patients contained in a public data set downloaded from GEO repository (GSE9891). Pearson correlation analyses were performed individually on EGFR, IL6, IL8 and PAI-1 (SERPINE1) expression intensities versus intensity of all the other genes in the data set. Correlation values and p-values of each pair were computed and p-values were adjusted for simple multiple testing procedures (“Bonferroni” and others) through the R programming language. This analysis yielded lists of candidate genes positively or negatively correlated to those of interest and, among those, 39 were in common among the genes correlated to IL6 and PAI-1. These genes were loaded in Ingenuity Pathway software and 23 genes resulted to be directly or indirectly associated with the “Cellular Movement, Embryonic Development, Cellular Growth and Proliferation” and “Skeletal and Muscular System Development and Function, Tissue Development” with the highest scores. Overall we identified a subtype of EGFR-expressing EOCs showing a particular signature of microenvironment-related genes thus facilitating the development of alternative approaches potentially suited for improving diagnosis and treatment of EOCs.

Partially supported by Italian Health Ministry (Grant ACC1)

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4930. doi:10.1158/1538-7445.AM2011-4930