Abstract
Abstract The analysis of quantitative protein expression is necessary for the determination of actual biochemical protein concentrations that can lead to a more accurate description of cellular function. A knowledgebase of cancer function founded on cellular protein levels can more directly implicate potential gene candidates for the detection and treatment of disease. Therefore, we analyzed iTRAQ (Isobaric tag for relative and absolute quantification) data from 11 serous ovarian cancer cell lines and 2 normal ovarian surface epithelial cell lines. We profiled cellular protein abundance in over 2600 proteins with 746 proteins common to all 13 cell lines. Of the 746, 52 proteins exhibited elevated expression and 46 proteins had diminished expression in the cancerous cells when compared to the two normal cell lines. We identified the 300 most variable iTRAQ expressed proteins based on median absolute deviation within 8 carboplatin sensitive and resistant cell lines. Using iTRAQ protein expression profiles from these 300 we successfully segregated the cell lines based on carboplatin sensitivity and resistance measurements. Next, we further examined correlations among iTRAQ protein expression, individual gene RNA expression and DNA methylation data. There was no substantial correlation between protein abundance and RNA expression or epigenetic data. Furthermore RNA expression and DNA methylation data alone did not show any significant discrimination for chemosensitivity or resistance. Our clustering proteomics-based profile used to identify chemotherapy response contained proteins involved in homologous recombination and repair, specifically RPA, MCM2/MCM5 and PALB2. We therefore present the potential of proteomics based discovery for carboplatin response in ovarian cancer and also identify putative gene candidates that may be functionally responsible for chemotherapy response which otherwise would not have been predicted by other singular whole genome data sources. Citation Format: Kazimierz O. Wrzeszczynski, Gaofeng Fan, Cexiong Fu, Darryl J. Pappin, Robert Lucito, Nicholas K. Tonks. Proteomic characterization of carboplatin resistance in ovarian cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B41.
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