Proteomic Analysis of Plasma in the Polycystic Ovary Syndrome Identifies Novel Markers Involved in Iron Metabolism, Acute-Phase Response, and Inflammation

CONTEXT: Hypothesis-free approaches such as proteomic analysis may identify novel biomarkers for disease. OBJECTIVE: The objective of the study was to compare the plasma proteome of patients presenting with the polycystic ovary syndrome (PCOS) with that of women without hyperandrogenism. DESIGN: This was a case-control study. SETTINGS: The study was conducted at an academic hospital. PATIENTS: Patients included 12 PCOS patients and 12 women without hyperandrogenism. INTERVENTIONS: Interventions included basal blood sampling. MAIN OUTCOME MEASURES: Two-dimensional difference in-gel electrophoresis, matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, Western blot, and ELISA analyses were measured. RESULTS: Two-dimensional difference in-gel electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry analyses identified haptoglobin beta-chain and alpha2-macroglobulin as proteins underexpressed in PCOS samples, whereas transferrin and kappa-free light chain were overexpressed. We were able to confirm only the underexpression of haptoglobin beta-chain in subsequent Western blot and ELISA analyses. CONCLUSIONS: Proteomic analysis of plasma from PCOS patients revealed changes in protein expression in several acute-phase response proteins including isoforms of plasma haptoglobin, alpha2-macroglobulin, and transferrin and in kappa-free light chain. In addition to their role as inflammatory markers, some of these molecules play major roles in iron metabolism, further suggesting that iron metabolism and low-grade chronic inflammation may be involved in the pathogenesis of insulin-resistant disorders such as PCOS.