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Identification of Ferroptosis-Inflammation Related Hub Genes and the Disease Subtypes in Idiopathic Pulmonary Fibrosis via System Biology Approaches

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Abstract

We aim to screen and analyze the ferroptosis inflammation-related hub genes associated with idiopathic pulmonary fibrosis (IPF). The GSE52463 and GSE110147 datasets were obtained from the GEO database and merged. The DEGs were selected by differential analysis and intersected with inflammation-related genes and ferroptosis-related genes to acquire the ferroptosis-related differentially expressed genes (FRDEGs). GO, KEGG, GSEA, and GSVA were performed to investigate the features of FRDEGs. The key module genes were selected by WGCNA and employed to generate the PPI network using Cytoscape. Subsequently, the hub genes were identified using cytoHubba and validated by ROC curves generated by survivalROC. Finally, the correlations of hub genes were analyzed through Spearman and the subtypes of IPF were constructed using ConsensusClusterPlus. A total of 1814 DEGs were screened out and 18 FRDEGs were acquired from the intersection of DEGs, ferroptosis-related genes, and inflammation-related genes. GO and KEGG analysis revealed that FRDEGs were primarily involved in bacterial-origin molecular, response infectious disease, and iron ion transport. GSEA results suggested a predominant association with autoimmune diseases and GSVA identified ten different pathways between PF and control. Through WGCNA, three highly correlated modules were identified and ten key module genes were obtained by intersecting genes in the three modules with FRDEGs. Finally, employing three algorithms within the cytoHubba led to the identification of eight hub genes: CCND1, TP53, STAT3, CTNNB1 CDH1, ESR1, HSP90AA1, and EP300. Eventually, two distinct subtypes of IPF were identified. The present research successfully identified the hub genes associated with ferroptosis and inflammation and their biological effects on IPF. Furthermore, two disease subtypes of IPF were constructed.

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Data and Materials Availability

The datasets used and/or analyzed during the current study are available from the corresponding author via email request.

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  1. Chongyang Niu and Xiaoyu Meng are the co-first authors.

Authors and Affiliations

  1. Changchun University of Chinese Medicine, No. 1035 Boshuo Road, Jingyue Economic Development district, Changchun, Jilin Province, 130000, China

    Chongyang Niu

  2. Lung Disease Center, The Affiliated Hospital of Changchun University of Chinese Medicine, No. 1478 Gongnong Road, Chaoyang District, Changchun, Jilin Province, 130000, China

    Chongyang Niu & Tan Wang

  3. Pediatric Center, The third affiliated hospital of Changchun university Chinese medicine, No. 1643 Jingyue Street, Nanguan District, Changchun, Jilin Province, 130000, China

    Xiaoyu Meng

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TW, CN and XM conceived and designed the experiments, CN, XM and TW performed the experiments and wrote the paper, CN and XM analyzed the data. All authors approved the final version. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Tan Wang.

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Supplemental Fig. 1

Eliminating Batch Effects in GSE52463 and GSE110147 Datasets. A The distribution of datasets before batch elimination. B The distribution of combined GEO datasets after batch elimination. C PCA plot before batch eliminating. D PCA plot of the combined GEO datasets after batch elimination. The dataset GSE110147 is represented in blue, while the dataset GSE52463 is depicted in red. PCA Principal component analysis, PF Pulmonary fibrosis

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Niu, C., Meng, X. & Wang, T. Identification of Ferroptosis-Inflammation Related Hub Genes and the Disease Subtypes in Idiopathic Pulmonary Fibrosis via System Biology Approaches. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01158-x

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