Abstract 3993: Characterisation of early ovarian cancer biomarkers

Around 22,000 new cases and 15,500 deaths from ovarian cancer are expected in the US in 2008, and currently women run an estimated 1/67 risk of developing ovarian cancer during their lifetime. Approximately 70% of patients present with late stage disease (stages III - IV; FIGO classification) and have a poor prognosis, with only a ∼30% 5 year survival rate. By contrast, patients diagnosed with early (stage I) disease exhibit survival rates above 90%, with disease often cured by surgery alone. The key issue is that early detection is hampered by a lack of sensitive and specific markers. The aim of this ongoing study was to apply 8-plex isobaric tags for relative and absolute quantitation (iTRAQ) for the proteomic investigation for early stage markers of ovarian cancer. Plasma was collected from patients and pooled as follows: G1-early stage cancers (stage I/II), G2-late stage cancers (stage III), G3-ascites fluid, G4-benign adenomas, G5-benign adenofibromas, G6-controls and G7-pool of all samples. Pooled patient samples were immuno-depleted of 12 abundant, disease-unrelated proteins and concentrated using reverse phase chromatography. Equal protein concentrations of each of the 7 pools were reduced, denatured, alkylated and digested using trypsin. Peptides from G1 through G7 were labelled with iTRAQ labels −113 to −119 respectively. Samples were combined and analysed using two-dimensional liquid chromatography (2D-LC) and mass spectrometry (4700 MALDI-TOF/TOF or QStar Elite, Applied Biosystems). Data were analysed using Protein Pilot (version 3.0, Applied Biosystems). Initial studies have identified 111 proteins with quantitation of 71 proteins, including numerous proteins that have been patented as candidate early markers for ovarian cancer. Of those identified, many are involved in inflammation/immunity and coagulation. Of considerable interest was the quantitative identification of numerous low abundance proteins not previously associated with early stage ovarian cancer. This proteome analysis has generated a catalogue of proteins that display potential as early markers for ovarian cancer. In addition, this study will assist in our understanding of the pathways potentially involved in the onset and progression of ovarian cancer. 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 3993.