Lee Moore

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NCI, DCEG, OEEB

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PLCO (Learn more about this study)

2006-0300

Early Detection of Ovarian Cancer Using Proteomic Analysis of Pre-diagnostic Serum Samples Collected in the PLCO Trial

Cancer is a disease of protein signaling pathways leading to uncontrolled cell growth and tissue differentiation. Proteins or protein fragments released by cancer cells and/or the tumor microenvironment that are present in blood could be used individually or in combination to discriminate diseased from healthy individuals. Previously we demonstrated that levels of post-translational modified forms of transthyretin were significantly different among cases compared to controls in blood serum samples collected from women hospitalized at the Mayo Clinic from 1980-1989 and stored in the National Cancer Institute Immunodiagnostic Serum Bank (Moore et al, CEBP 2006). We found that: i.) levels of six forms of transthyretin were significantly different in women with ovarian cancer than those diagnosed with benign ovarian cysts or digestive diseases; ii) the specificity of transthyretin markers and apolipoprotein A1 was 96.5% but sensitivity was low, 52.4%, and iii) all seven markers (six forms of transthyretin plus apolipoprotein A1) in combination with CA125 had 94.3% specificity and 78.6% sensitivity. Thus, our findings reproduced the results by Zhang at al. (2004) in the Mayo samples. In the proposed study, we will compare levels of the same markers in serum collected among women diagnosed with early stage ovarian cancer and women in three control groups enrolled in the PLCO screening trial. We also propose to include additional markers from our discovery work (NCI, Ciphergen Inc) and from a recent paper by Mor et al., PNAS 2005. Our marker panel should significantly improve the sensitivity and specificity of CA125 for early detection of ovarian cancer.