Comparative Study of Circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as Disease Markers of Idiopathic Pulmonary Fibrosis

Abstract

Background. Recent reports indicate that matrix metalloproteinase-7 (MMP-7) and CC-chemokine ligand 18 (CCL18) are potential disease markers of idiopathic pulmonary fibrosis (IPF). The objective of this study was to perform direct comparisons of these two biomarkers with three well-investigated serum markers of IPF, Krebs von den Lungen-6 (KL-6), surfactant protein-A (SP-A), and SP-D. Methods. The serum levels of MMP-7, CCL18, KL-6, SP-A, and SP-D were evaluated in 65 patients with IPF, 31 patients with bacterial pneumonia, and 101 healthy controls. The prognostic performance of these five biomarkers was evaluated in patients with IPF. Results. The serum levels of MMP-7, KL-6, and SP-D in patients with IPF were significantly elevated compared to those in patients with bacterial pneumonia and in the healthy controls. Multivariate survival analysis showed that serum MMP-7 and KL-6 levels were independent predictors in IPF patients. Moreover, elevated levels of both KL-6 and MMP-7 were associated with poorer survival rates in IPF patients, and the combination of both markers provided the best risk discrimination using the C statistic. Conclusions. The present results indicated that MMP-7 and KL-6 were promising prognostic markers of IPF, and the combination of the two markers might improve survival prediction in patients with IPF.

Figure 1

Serum levels of (a) MMP-7, (b) CCL18, (c) KL-6, (d) SP-A, and (e) SP-D in patients with IPF, those with bacterial pneumonia (BP), and healthy controls (HC). The significant differences between the three groups were evaluated using Bonferroni's test (^∗ p < 0.01 and ^∗∗ p < 0.001).

Figure 2

ROC curve analysis in five biomarkers to distinguish IPF patients from control subjects which consisted of patients with bacterial pneumonia and healthy controls.

Figure 3

Kaplan-Meier analysis to evaluate the probability of 5-year survival among the three groups which were divided according to the serum levels of KL-6 and MMP-7. The cut-off levels of KL-6 and MMP-7 were 1040 U/mL and 9.67 ng/mL, respectively. The probability of 5-year survival was significantly different among them (p = 0.0004).