AUTHOR=Li Meng , Wang Ke , Zhang Yanpeng , Fan Meng , Li Anqi , Zhou Jiejun , Yang Tian , Shi Puyu , Li Dan , Zhang Guangjian , Chen Mingwei , Ren Hui 

TITLE=Ferroptosis-Related Genes in Bronchoalveolar Lavage Fluid Serves as Prognostic Biomarkers for Idiopathic Pulmonary Fibrosis

JOURNAL=Frontiers in Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.693959

DOI=10.3389/fmed.2021.693959

ISSN=2296-858X

ABSTRACT=Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease with unknown etiology and unfavorable prognosis. Ferroptosis is a form of regulated cell death with an iron-dependent way that is involved in the development of various diseases. Whereas, the prognostic value of ferroptosis-related genes (FRGs) in IPF remains uncertain and needs to be further elucidated.
Methods: FerrFb database and previous studies were screened to explore the FRGs. The data of IPF patients were obtained from the GSE70866 dataset. Wilcoxon test and univariate Cox regression analysis were applied to identify the FRGs that are differentially expressed between normal and IPF patients and associated with prognosis. Next, a multigene signature was constructed by the Lasso-penalized cox model in the training cohort and evaluated by using calibration and receiver operating characteristic (ROC) curves. Then, 30% of the dataset samples were randomly selected for internal validation. Finally, the potential function and pathways that might affect by the risk score-related differently expressed genes (DEGs) were further explored.
Results: 183 FRGs were identified by the FerrFb database and previous studies, and 19 of them were differentially expressed in bronchoalveolar lavage fluid (BALF) between IPF and healthy controls and associated with prognosis (P<0.05). 5-FRGs (ACO1, NRAS, ENPP2, MUC1, ZFP36) were identified as risk signatures and stratified patients with IPF into two risk groups. The overall survival rate in patients with high risk was significantly lower than that in patients with low risk (P<0.001). Calibration and ROC curve analysis confirmed the predictive capacity of this signature, and the results were further verified in the validation group. Risk score-related DEGs were found enriched in ECM-receptor interaction and focal adhesion pathways. 
Conclusion: The 5 FRGs in BALF can be used for prognostic prediction in IPF, which may contribute to improving management strategies of IPF.