Abstract 1995: Expression profiling of microdissected serous ovarian cancers and matched Fallopian tube identifies a gene signature of clinicopathologic importance

Abstract

Abstract Recent evidence on the “fallopian tube as a site of origin for ovarian tumors” has increased the effort to identify the molecular events associated with initiation and progression of this type of tumor. The aim of this study is to generate a gene expression signature for microdissected serous ovarian carcinoma and matched benign fallopian tube epithelium from the samples obtained from women with high grade serous ovarian cancer at the time of surgery at Brigham and Women's Hospital. All patient specimens were collected and studied under protocols approved by the institutional review board of the parent institution. Gene expression profiling was performed using Affymetrix Human Genome U133 Plus 2.0 array platform between serous ovarian cancer (SOC) versus their matched tubal epithelial counterparts (MTC). MAS5.0 normalized data was checked to ensure scaling factors and array controls were within normal bounds. Data filtering restricted the analysis to transcripts called present in at least 50% of the arrays and displaying a variance in the top 50th percentile. The 17,379 probe sets meeting these criteria were imported into BRB-ArrayTools. Unsupervised hierarchical clustering of the 18 arrays using a centered correlation and average linkage revealed a dendrogram that with 2 distinct branches that clearly distinguished SOC and MTC. Differentially expressed genes were identified for SOC and MTC specimens using a paired T-test (p<0.001) with a random variance model. We identified 1821 genes (725 up- and 1096 down-regulated) that were differentially expressed between all 9 SOC and MTC pairs. The microarray data was validated using quantitative reverse transcription polymerase chain reaction on 8 randomly selected differentially regulated genes. 7/8 (87.5%) genes showed robust correlations between microarray and qRT-PCR expression data. Gene ontology analysis indicated biological processes of transport, glycolysis, apoptosis, signal transduction, fat cell differentiation, and cell proliferation. 91 genes were found to be associated with ATP biosynthetic process (p:-0.00241), 25 genes were associated with regulation of apoptosis (p: 0.00014), 40 genes were associated with steroid hormone receptor activity (p: 0.00041). Further data mining for biologically relevant processes using Pathway Studio 6.0 identified genes overexpressed in SOC that were related to the peroxisome proliferator-activated receptors (PPARs). FABP5, SCD, SLC27A6, PCK2, ACSL5, DUSP1, GK, NR2F1 were found to be differentially regulated in SOC, implicates the role PPAR signaling pathway in initiation / progression of SOC. In conclusion, we generated an expression profile from serous ovarian carcinomas and matched fallopian tube mucosa, and which will help to formulate better strategies for predicting disease outcome, so that the treatments can be targeted more effectively. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1995.