S100A12 as Biomarker of Disease Severity and Prognosis in Patients With Idiopathic Pulmonary Fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is one of interstitial lung diseases (ILDs) with poor prognosis. S100 calcium binding protein A12 (S100A12) has been reported as a prognostic serum biomarker in the IPF, but its correlation with IPF remains unclear in the lung tissue and bronchoalveolar lavage fluids (BALF).

Methods: Datasets were collected from the Gene Expression Omnibus (GEO) database. Person correlation coefficient, Kaplan-Meier analysis, Cox regression analysis, functional enrichment analysis and so on were used. And single cell RNA-sequencing (scRNA-seq) analysis was also used to explore the role of S100A12 and related genes in the IPF.

Results: S100A12 was mainly and highly expressed in the monocytes, and its expression was downregulated in the lung of patients with IPF according to scRNA-seq and the transcriptome analysis. However, S100A12 expression was upregulated both in blood and BALF of patients with IPF. In addition, 10 genes were found to interact with S100A12 according to protein-protein interaction (PPI) network, and the first four transcription factors (TF) targeted these genes were found according to hTFtarget database. Two most significant co-expression genes of S100A12 were S100A8 and S100A9. The 3 genes were significantly negatively associated with lung function and positively associated with the St. George's Respiratory Questionnaire (SGRQ) scores in the lung of patients with IPF. And, high expression of the 3 genes was associated with higher mortality in the BALF, and shorter transplant-free survival (TFS) and progression-free survival (PFS) time in the blood. Prognostic predictive value of S100A12 was more superior to S100A8 and S100A9 in patients with IPF, and the composited variable [S100A12 + GAP index (gender, age, and physiological index)] may be a more effective predictive index.

Conclusion: These results imply that S100A12 might be an efficient disease severity and prognostic biomarker in patients with IPF.