Identification and validation of SPP1 as a prognostic biomarker in interstitial lung disease subtypes by single-cell
Tong Ji1,2, Yuting Li3, Shenao Zhang3
1Department of Pulmonary and Critical Care Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Interstitial lung diseases (ILDs) are a heterogeneous group of disorders with diverse clinical trajectories, highlighting the need for reliable biomarkers for prognostic assessment and risk stratification.
Methods:
Single-cell RNA sequencing (scRNA-seq) was performed on explanted lung tissue from 3 patients with idiopathic pulmonary fibrosis (IPF) and 3 control subjects. Secreted phosphoprotein 1 (SPP1) was identified and further validated in serum samples from two ILD cohorts comprising 74 patients with IPF and 92 with idiopathic inflammatory myopathy-associated ILD (IIM-ILD), as well as 56 healthy controls (HCs). Patients with IPF were further classified as acute exacerbation (AE) or stable IPF, and patients with IIM-ILD as rapidly progressive (RP) or stable IIM-ILD. The association between serum SPP1 levels and 1-year all-cause mortality was assessed using Cox proportional hazards models.
Results:
scRNA-seq demonstrated that SPP1 expression was markedly upregulated in explanted lungs from IPF patients compared with controls. Serum SPP1 levels were significantly higher in patients with ILD than in HCs (P < 0.001), and were further elevated in AE-IPF (P < 0.001), RP-IIM-ILD (P < 0.001), and anti-melanoma differentiation-associated gene 5-positive IIM-ILD (P = 0.015). The 1-year mortality rates were 35.1% in patients with IPF and 31.5% in those with IIM-ILD. In multivariable Cox analyses, serum SPP1 was an independent predictor of 1-year mortality in the overall ILD cohort (hazard ratio [HR] 1.007, 95% confidence interval [CI] 1.002-1.012, P = 0.005), as well as in the IPF (HR 1.015, 95% CI 1.003-1.027, P = 0.012) and IIM-ILD (HR 1.007, 95% CI 1.001-1.012, P = 0.022) subgroups.
Conclusions:
Serum SPP1 may serve as a potential biomarker for risk stratification and prognostic assessment in IPF and IIM-ILD.