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Proteomic Profiling Identifies Afamin as a Potential Biomarker for Ovarian Cancer

Authors' Affiliations: ¹ Cancer Research UK Clinical Centre, ² Department of Obstetrics and Gynaecology, and ³ Department of Pathology, St James's University Hospital, Leeds, United Kingdom; ⁴ Discovery Enabling Capabilities and Sciences, AstraZeneca, Alderley Park, United Kingdom; ⁵ Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, and ⁶ Department of Gynecology and Obstetrics, Innsbruck Medical University; ⁷ Vitateq Biotechnology GmbH, Innsbruck, Austria; ⁸ Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria; and ⁹ Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford, United Kingdom

Requests for reprints: Rosamonde Banks, Cancer Research UK Clinical Centre, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, United Kingdom. Phone: 44-113-2064927; Fax: 44-113-2429886; E-mail: R.Banks{at}leeds.ac.uk.

Purpose: To discover and validate serum glycoprotein biomarkers in ovarian cancer using proteomic-based approaches.

Experimental Design: Serum samples from a "discovery set" of 20 patients with ovarian cancer or benign ovarian cysts or healthy volunteers were compared by fluorescence two-dimensional differential in-gel electrophoresis and parallel lectin-based two-dimensional profiling. Validation of a candidate biomarker was carried out with Western blotting and immunoassay (n = 424).

Results: Twenty-six proteins that changed significantly were identified by mass spectrometric sequencing. One of these, confirmed by Western blotting, was afamin, a vitamin E binding protein, with two isoforms decreasing in patients with ovarian cancer. Validation using cross-sectional samples from 303 individuals (healthy controls and patients with benign, borderline, or malignant ovarian conditions and other cancers) assayed by ELISA showed significantly decreased total afamin concentrations in patients with ovarian cancer compared with healthy controls (P = 0.002) and patients with benign disease (P = 0.046). However, the receiver operating characteristic areas for total afamin for the comparison of ovarian cancer with healthy controls or benign controls were only 0.67 and 0.60, respectively, with comparable figures for CA-125 being 0.92 and 0.88 although corresponding figures for a subgroup of samples analyzed by isoelectric focusing for afamin isoform 2 were 0.85 and 0.79. Analysis of a further 121 samples collected prospectively from 9 patients pretreatment through to relapse indicated complementarity of afamin with CA-125, including two cases in whom CA-125 was noninformative.

Conclusions: Afamin shows potential complementarity with CA-125 in longitudinal monitoring of patients with ovarian cancer, justifying prospective larger-scale investigation. Changes in specific isoforms may provide further information.