An 8-ferroptosis-related genes signature from Bronchoalveolar Lavage Fluid for prognosis in patients with idiopathic pulmonary fibrosis

Abstract

Background With 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. Methods Datasets 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. Results Nineteen 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. Conclusions These 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.

Construction and Validation of a Novel Prognostic Signature of Idiopathic Pulmonary Fibrosis by Identifying Subtypes Based on Genes Related to 7-Methylguanosine Modification

“…Furthermore, the nomogram established in our study revealed the critical potential clinical significance of m7GPS by accurately predicting the short-term survival of IPF patients. Additionally, we confirmed that m7GPS and its constituent genes were reliable indicators for screening IPF patients from healthy individuals, while similar investigations were not discussed by the prognostic signatures of Prasse et al (2019) , Li et al (2021) , He et al (2022) . In conclusion, the m7GPS constructed in our study may serve as a novel biomarker for predicting the prognosis of IPF patients and screening IPF patients.…”

“…m7GPS was an independent risk factor for the prognosis of IPF patients. The accuracy of m7GPS in predicting the 1-, 3-, and 5-year survival status of IPF patients was higher than that of the ferroptosis-related signatures constructed by Li et al (2021) , He et al (2022) . Moreover, compared to the signature identified by Prasse et al (2019) , the concordance indexes (0.76–0.80) of GAP stages combined with m7GPS were slighter higher than that (0.71–0.78) of GAP stages combined with the signature of Prasse et al (2019) , which suggested the advantage of m7GPS to some extent.…”

“…Our study highlighted the association of the four genes with poor prognosis of IPF patients according to univariate Cox regression analysis results. Indeed, three prognosis signatures have been established by the recent studies of Prasse et al (2019) , Li et al (2021) , He et al (2022) . All of their prognosis signatures could be used to predict the prognosis of IPF patients.…”

Role of Ferroptosis in Fibrotic Diseases

“…13,112 Bioinformatics analysis also supported that ferroptosis-related genes are significantly correlated with the development of IPF. [113][114][115] Moreover, some ferroptosis-related genes in the bronchoalveolar lavage showed prognostic value in patients with IPF. 113,115 Current studies mainly focus on the role of ferroptosis in the alveolar epithelial injury, fibroblast-to-myofibroblast transition, and epithelial-mesenchymal transition (EMT), all of which are important biological processes in the development of IPF.…”

“…[113][114][115] Moreover, some ferroptosis-related genes in the bronchoalveolar lavage showed prognostic value in patients with IPF. 113,115 Current studies mainly focus on the role of ferroptosis in the alveolar epithelial injury, fibroblast-to-myofibroblast transition, and epithelial-mesenchymal transition (EMT), all of which are important biological processes in the development of IPF. It is now established that dysfunction of alveolar epithelial cells, especially alveolar type 2 (AT II) cells, drive the pathogenesis of IPF.…”