Abstract
Biomarkers for the progression of lung function in COPD are currently scarce. Plasma fetuin-B (FETUB) was identified by iTRAQ-based proteomics and was verified by ELISA in another group. Information regarding acute exacerbation (AE) was collected in a one-year follow-up programme. FETUB concentrations (1652 ± 427 ng/ml) were greater in COPD patients than in controls (1237 ± 77 ng/ml). The concentrations of FETUB in GOLD II (1762 ± 427 ng/ml), III (1650 ± 375 ng/ml) and IV (1800 ± 451 ng/ml) groups were greater than those in the controls (1257 ± 414 ng/ml) and the GOLD I (1345 ± 391 ng/ml) group. ROCs indicated that FETUB distinguished COPD patients from controls (AUC 0.747, 95% CI: 0.642–0.834) and also GOLD II, III and IV from GOLD I COPD patients (AUC: 0.770, 95% CI: 0.634–0.874). The combination of FETUB and fibrinogen performed better (AUC: 0.804, 95% CI: 0.705–0.881). FETUB also predicted the occurrence of AE (AUC: 0.707, 95% CI: 0.566–0.824) or frequent AE (AUC: 0.727, 95% CI: 0.587–0.840). FETUB concentrations were negatively correlated with FEV1%pred (r = −0.446, p = 0.000) and positively correlated with RV%pred (r = 0.317, p = 0.004), RV/TLC% (r = 0.360, p = 0.004), CT emphysema% (r = 0.322, p = 0.008) and grades of lung function (r = 0.437, p = 0.000). In conclusion, FETUB is likely to assist the diagnosis and management of COPD as a complement for other markers.
Highlights
Proteomics-based biomarker studies in the Chronic obstructive pulmonary disease (COPD) field are mainly focused on gel-based[11,14], targeted[16,17] and labeling-free[9,10,15] proteomic techniques
The difference of FETUB between the GOLD I group (1345 ± 391 ng/ml) and the GOLD III group (1650 ± 375 ng/ml) were not significant statistically, which may have been due to the lack of statistical power
Plasma FETUB was identified in COPD by the gel-free isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic technique
Summary
Proteomics-based biomarker studies in the COPD field are mainly focused on gel-based[11,14], targeted[16,17] and labeling-free[9,10,15] proteomic techniques. The gel-free isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic technique, an isotope-labelling and untargeted approach, have been used in the COPD field[18]. The technique has not been used to investigate plasma biomarkers related to the clinically stable stage of COPD. We tried to identify plasma biomarkers for the progression of lung function in COPD by the gel-free iTRAQ-based proteomic technique. To further verify and investigate the clinical value of these biomarker candidates identified in the discovery group by the proteomics, we measured their levels in plasma in a larger population by enzyme-linked immuno sorbent assay (ELISA)
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