Soluble ST2 in serum predicts the prognosis of idiopathic pulmonary fibrosis: a retrospective study

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a heterogeneous and progressive fibrosing interstitial lung disease with a poor prognosis. However, there are currently no effective biomarker that can reliably predict the prognosis for IPF in clinic. The serum level of soluble suppression of tumorigenicity-2 (sST2), which is involved in the immune response, has proven to be a prognostic predictor for various diseases.Previous studies have confirmed that the immune dysfunction plays an important role in the pathogenesis of IPF and the serum sST2 concentrations in patients with IPF are elevated. However, the relationship between sST2 and the prognosis of IPF remains unknown.Methods: A total of 83 patients with IPF and 20 healthy controls from 2016 to 2021 were enrolled and demographic variables, indices of lung function testing as well as the biomarkers including the sST2 were obtained at baseline. During follow-up, the primary endpoint was defined as all-cause death and clinical deterioration. Cox hazard models and Kaplan-Meier method were used to assess the prognostic value of various indices including sST2.Results: Mean duration of follow-up was 29 months, during which 49 patients had an event, and of them, 35 patients died. The sST2 level was higher in the IPF patients compared with the healthy controls.Although the sST2 level did not directly predict all-cause death in the present study, it was proved to be an independent predictor of event-free survival. Multivariate forward stepwise model which was adjusted by age, sex, and body surface area (BSA) showed that the overexpression of sST2 increased the hazard ratio [1.005, 95% confidence interval (CI): 1.001-1.010]. A higher sST2 serum level heralded more deterioration and the poor outcomes. Moreover, the effect of sST2 on the prognosis of IPF may not necessarily involve the development of IPF-related pulmonary hypertension (PH).Conclusions: In our study, the sST2 serum level was significantly elevated and a higher serum level of sST2 predicted more deterioration and poor outcomes in patients with IPF. Thus, sST2 can serve as a valuable prognostic biomarker for the outcome of IPF. However, further multicenter clinical trials of larger sample size are needed in the future.

Current Trends in Biohumoral Screening for the Risk of Sudden Cardiac Death: A Systematic Review

“…The authors recommended using ST2 as an additional marker in the diagnosis of heart failure [ 87 ]. Elevated levels of ST2 as a negative prognostic factor can also be found in myelodysplastic syndrome [ 88 ], pulmonary hypertension [ 89 ], ulcerative colitis [ 90 ], and idiopathic pulmonary fibrosis [ 91 ].…”

Predictive biomarkers of disease progression in idiopathic pulmonary fibrosis

“…Suppression of thrombogenicity-2 (ST2) is a member of the interleukin-1 (IL-1) receptor family, and soluble ST2 in serum is an independent predictor of event-free survival of IPF patients. While soluble ST2 cannot directly predict the all-cause mortality of IPF patients, a higher level of serum soluble ST2 is associated with a worse outcome of IPF patients [ 72 ]. To determine the impact of soluble ST2 on the prognosis of IPF, additional multicenter, large sample quantity, and quantitative studies are needed.…”

Antifibrotic Drugs against Idiopathic Pulmonary Fibrosis and Pulmonary Fibrosis Induced by COVID-19: Therapeutic Approaches and Potential Diagnostic Biomarkers

“…Thus, the importance of these biomarkers becomes evident for their future validation and application to FP. sITGaM (soluble integrin subunit alpha M), sITGb2 (soluble integrin subunit beta 2), m5CPS (5-methylcytosine), IL13RA2 (interleukin 13 receptor subunit alpha 2), CDH3 (cadherin 3), COMP (cartilage oligomeric matrix protein), ET-1 (endothelin-1), CRTAC1 (cartilage acid protein 1), COL10A1 (collagen type X alpha 1), IGFL2 (like family member 2), NECAB1 (N-terminal EF-hand calcium binding protein 1), SCG5 (secretogranin V), SLC6A4 (solute carrier family 6 member 4), SPP1 (secreted phosphoprotein 1), B4GALT1 (beta-1,4-galactosyltransferase), GDF-15 (growth differentiation factor 15), CYFRA21 (cytokeratin fragment 19), RBM11 (RNA-binding motif protein 11), RIC3 (resistance to inhibitors of cholinesterase 3), TRAF5 (TNF receptor-associated factor 5), ZNF14 (zinc finger protein 14), RBM47 (RNA-binding motif protein 47), IL1R2 (interleukin 1 receptor type 2), S100A12 (S100 calcium binding protein A12), CCL8 (C-C motif chemokine ligand 8), sST2 (soluble receptor form 2), TPST1 (tyrosyl protein sulfotransferase 1), MRVI1 (inositol 1,4,5-triphosphate receptor associated 1), TMF4S1 (transmembrane 4 L six family member 1), HE4 (human epididymis protein 4) [148][149][150][151][152][153][154][155][156][157][158][159][160]. Other potential biomarkers are also shown to predict the prognosis of patients with FP, such as the use of RBM11, which, if overexpressed, is an indicator of a good prognosis for patients, while if RBM47 is overexpressed, it is an indicator of a poor prognosis for patients.…”

“…sST2 Serum [157] ST2: belongs to the interleukin-1 (IL-1) receptor family, which exists in transmembrane (ST2L) and soluble (sST2) isoforms.…”