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

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.