Abstract
BackgroundWith the rapid advances of genetic and genomic technologies, the pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) were gradually becoming clear, however, the prognosis of IPF was still poor. This study aimed to systematically explore the ferroptosis-related genes model associated with prognosis in IPF patients.MethodsDatasets were collected from the Gene Expression Omnibus (GEO). The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was applied to create a multi-gene predicted model from patients with IPF in the Freiburg cohort of the GSE70866 dataset. The Siena cohort and the Leuven cohort were used for validation.ResultsNineteen differentially expressed genes (DEGs) between the patients with IPF and control were associated with poor prognosis based on the univariate Cox regression analysis (all P < 0.05). According to the median value of the risk score derived from an 8-ferroptosis-related genes signature, the three cohorts’ patients were stratified into two risk groups. Prognosis of high-risk group (high risk score) was significantly poorer compared with low-risk group in the three cohorts. According to multivariate Cox regression analyses, the risk score was an independently predictor for poor prognosis in the three cohorts. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) confirmed the signature's predictive value in the three cohorts. According to functional analysis, inflammation- and immune-related pathways and biological process could participate in the progression of IPF.ConclusionsThese results imply that the 8-ferroptosis-related genes signature in the bronchoalveolar lavage samples might be an effective model to predict the poor prognosis of IPF.
Highlights
Characterized by fibrosis or structural deformations, idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown etiology [1, 2]
Identification of prognostic ferroptosis‐related differentially expressed genes (DEGs) in the Freiburg cohort Of the 293 ferroptosis-related genes, 51 (17.4%) were differentially expressed between patients with IPF and controls, and 19 of them were correlated with prognosis according to the univariate Cox regression analysis (Fig. 2a–c)
Construction of a prognostic model in the Freiburg cohort A prognostic model was established by least absolute shrinkage and selection operator (LASSO) Cox regression analysis using the expression profile of the 19 genes mentioned above
Summary
Characterized by fibrosis or structural deformations, idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown etiology [1, 2]. In the United States, incidence of IPF in people aged 18–64 years was 6.1 new cases per 100,000 person-years [3]. Pirfenidone and nintedanib have been approved by the United States Food and Drug Administration to treat patients with IPF [4, 5]. No of patients Age (median, range) Gender (%) Female male GAP Stage I Stage II Stage III Survival status Time to death (months) Censored 62 69 (63–75) 18 (6–32) 17 (27.4) 14 ± 9 19 (38.0) 12 (7–24). With the rapid advances of genetic and genomic technologies, the pathophysiological mechanisms of idiopathic pulmonary fibrosis (IPF) were gradually becoming clear, the prognosis of IPF was still poor. This study aimed to systematically explore the ferroptosis-related genes model associated with prognosis in IPF patients
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