Prognostic significance of peripheral blood S100A12, S100A8, and S100A9 concentrations in idiopathic pulmonary fibrosis

Dongyan Ding; Rumei Luan; Qianfei Xue; Junling Yang

doi:10.1016/j.cyto.2023.156387

Prognostic significance of peripheral blood S100A12, S100A8, and S100A9 concentrations in idiopathic pulmonary fibrosis

Cytokine. 2023 Dec:172:156387. doi: 10.1016/j.cyto.2023.156387. Epub 2023 Oct 10.

Authors

Dongyan Ding¹, Rumei Luan¹, Qianfei Xue², Junling Yang³

Affiliations

¹ Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, China.
² Department of Respiratory Medicine, The University Hospital of Jilin University, Changchun, China.
³ Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, China. Electronic address: junling@jlu.edu.cn.

PMID: 37826869
DOI: 10.1016/j.cyto.2023.156387

Abstract

Background: S100A12, S100A8, and S100A9 are inflammatory disease biomarkers whose functional significance in idiopathic pulmonary fibrosis (IPF) remains unclear. We evaluated the significance of S100A12, S100A8, and S100A9 levels in IPF development and prognosis.

Methods: The dataset was collected from the Gene Expression Omnibus (GEO) database and differentially expressed genes were screened using GEO2R. We conducted a retrospective study of 106 patients with IPF to explore the relationships between different biomarkers and poor outcomes. Pearson's correlation coefficient, Kaplan-Meier, Cox regression, and functional enrichment analyses were used to evaluate relationships between these biomarkers' levels and clinical parameters or prognosis.

Results: Serum levels of S100A12, S100A8, and S100A9 were significantly elevated in patients with IPF. The two most significant co-expression genes of S100A12 were S100A8 and S100A9. Patients with levels of S100A12 (median 231.21 ng/mL), S100A9 (median 57.09 ng/mL) or S100A8 (median 52.20 ng/mL), as well as combined elevated S100A12, S100A9, and S100A8 levels, exhibited shorter progression-free survival and overall survival. Serum S100A12 and S100A8, S100A12 and S100A9, S100A9 and S100A8 concentrations also displayed a strong positive correlation (r_s² = 0.4558, r_s² = 0.4558, r_s² = 0.6373; P < 0.001). S100A12 and S100A8/9 concentrations were independent of FVC%, DLCO%, and other clinical parameters (age, laboratory test data, and smoking habit). Finally, in multivariate analysis, the serum levels of S100A12, S100A8, and S100A9 were significant prognostic factors (hazard ratio 1.002, P = 0.032, hazard ratio 1.039, P = 0.001, and hazard ratio 1.048, P = 0.003).

Conclusions: S100A12, S100A8, and S100A9 are promising circulating biomarkers that may aid in determining IPF patient prognosis. Multicenter clinical trials are needed to confirm their clinical value.

Keywords: Calgranulin; S100A12; S100A8; S100A9; idiopathic pulmonary fibrosis (IPF).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Calgranulin A / genetics
Calgranulin B / genetics
Humans
Idiopathic Pulmonary Fibrosis* / genetics
Prognosis
Retrospective Studies
S100A12 Protein*

Substances

Biomarkers
Calgranulin A
Calgranulin B
S100A12 Protein
S100A12 protein, human