Clinical significance of serum S100 calcium‐binding protein A4 in idiopathic pulmonary fibrosis

Abstract

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. There are no established serum biomarkers for predicting the outcomes of IPF. S100 calcium-binding protein A4 (S100A4) is considered as a marker of fibroblasts; however, its clinical application remains to be investigated. We evaluated the clinical relevance of S100A4 in IPF patients. METHODS: Serum S100A4 levels in 95 consecutive IPF patients and 50 healthy controls (HC) were measured using enzyme-linked immunosorbent assay. S100A4 expression in lung tissues was determined using immunohistochemistry/immunofluorescence and its association with disease progression (defined as deterioration in lung function or death) and mortality was assessed using Kaplan-Meier method and Cox hazards analysis. RESULTS: Serum S100A4 levels were undetectable in all HC but were detectable in 26 (27.3%) of the 95 IPF patients (P < 0.01). Immunostaining of lung tissues from IPF patients showed aggregation of numerous S100A4-expressing cells around the fibroblastic foci and mature fibrotic regions. IPF patients with higher serum S100A4 levels had a significantly worse prognosis than those with low serum levels (2-year cumulative survival rate: 41.7% vs 77.0%, respectively, P < 0.01). On multivariate analyses, baseline serum S100A4 levels (per 10 ng/mL increase) were independently associated with higher disease progression rate (odds ratio: 1.06, P = 0.01) and higher mortality (hazard ratio: 1.18, P = 0.03). CONCLUSION: S100A4 is a promising serum biomarker that may help predict disease progression/mortality. Our findings may help establish treatment strategies for IPF.