AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.4101
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ORIGINAL RESEARCH ARTICLE

Bioinformatics analysis of therapeutic targets for idiopathic pulmonary fibrosis and exploration of immune cell infiltration patterns

Zhendong Lu1 ,  Umair Ali Khan Saddozai2 ,  Siyun Fu1 ,  Lingqin Zhu3 ,  Jinghui Wang1,3*
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1 Department of Medical Oncology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China
2 Department of Clinical Medicine, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, China
3 Cancer Research Center, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, China
GPD, 4101 https://doi.org/10.36922/gpd.4101
Submitted: 1 July 2024 | Accepted: 13 August 2024 | Published: 10 October 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Idiopathic pulmonary fibrosis (IPF) is a severe progressive lung disease characterized by fibrotic changes in lung tissue, with limited treatment options. This study analyzed gene expression data from three gene expression omnibus datasets (GSE2052, GSE53845, and GSE110147) using R and LIMMA to identify differentially expressed genes (DEGs) in IPF samples. We identified 215 DEGs, comprising 106 upregulated and 109 downregulated genes. Weighted gene coexpression network analysis revealed five gene modules, with the module eigengene yellow showing the strongest correlation with IPF. Functional enrichment analysis of 40 consensus genes in this module indicated their significant involvement in extracellular matrix (ECM) organization. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed pathways related to protein digestion, cell adhesion molecules, and the advanced glycation end product–receptor for advanced glycation end product signaling pathway. Based on protein–protein interaction network analysis, collagen type XV alpha 1 chain (COL15A1) and collagen type VI alpha 3 chain (COL6A3) were identified as upregulated hub genes in IPF, which were regulated by microRNAs and transcription factors. Immune cell infiltration analysis showed significant changes in immune cell populations in IPF samples, with increases in memory B cells, plasma cells, and M0 macrophages and decreases in CD8 T cells, and resting natural killer cells. Potential drugs targeting COL15A1 and COL6A3 were predicted using multiple databases, revealing compounds such as (+)-JQ1, aristolochic acid I, and dexamethasone with promising binding potential. These findings suggest that COL15A1 and COL6A3 are central hub genes in IPF, are associated with ECM organization and immune response, and serve as therapeutic targets for IPF.

Keywords
Idiopathic pulmonary fibrosis
Weighted gene coexpression network analysis
Immune cell infiltration
MicroRNA-transcription factor-mRNA network
Molecular docking
Funding
The work was supported by the Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (PWD&RPP-MRI; Project Number: JYY2023-14).
Conflict of interest
Umair Ali Khan Saddozai serves as the Editorial Board Member of the journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
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