Isoform 1 of Fibrinogen Alpha Chain Precursor is a Potential Biomarker for Steroid-Induced Osteonecrosis of the Femoral Head.

ABSTRACT

PURPOSE: Early diagnosis is crucial to increase the chances of conservation treatment for patients with steroid-induced osteonecrosis of the femoral head (SIONFH). This study aimed to identify serum peptides as potential biomarkers to diagnose SIONFH. EXPERIMENTAL DESIGN: The serum proteome of 32 SIONFH patients and 24 healthy controls are analyzed using magnetic bead-based weak cation exchange (MB-WCX) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS). Next, candidate biomarkers are identified using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Candidate biomarkers are then validated using ELISA and western blotting. RESULTS: 39 peaks are identified and the expression fold changes of seven peaks in the two groups are greater than 1.5. Three peaks (m/z 1077.84 Da; m/z 1061.78 Da; m/z 1099.56 Da) tend to be upregulated, while four peaks (m/z 3973.92 Da; m/z 7766.53 Da; m/z 3957.31 Da; m/z 4212.02 Da) tend to be down-regulated in SIONFH patients. The peak for a 1077.84 Da peptide is identified as Isoform 1 of the Fibrinogen alpha chain precursor (FGA). ELISAs and western blot analyses reveal that the expression of FGA is significantly higher in SIONFH patients than healthy controls. CONCLUSION AND CLINICAL RELEVANCE FGA is overexpressed in SIONFH patients, and thus, is a novel potential biomarker for SIONFH.