Transcriptomics in idiopathic pulmonary fibrosis unveiled: a new perspective from differentially expressed genes to therapeutic targets
BackgroundThe underlying molecular pathways of idiopathic pulmonary fibrosis (IPF), a progressive lung condition with a high death rate, are still mostly unknown. By using microarray datasets, this study aims to identify new genetic targets for IPF and provide light on the genetic factors that contr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1375171/full |
| _version_ | 1797257638720831488 |
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| author | Wenzhong Hu Yun Xu |
| author_facet | Wenzhong Hu Yun Xu |
| author_sort | Wenzhong Hu |
| collection | DOAJ |
| description | BackgroundThe underlying molecular pathways of idiopathic pulmonary fibrosis (IPF), a progressive lung condition with a high death rate, are still mostly unknown. By using microarray datasets, this study aims to identify new genetic targets for IPF and provide light on the genetic factors that contribute to the development of IPF.MethodWe conducted a comprehensive analysis of three independent IPF datasets from the Gene Expression Omnibus (GEO) database, employing R software for data handling and normalization. Our evaluation of the relationships between differentially expressed genes (DEGs) and IPF included differential expression analysis, expression quantitative trait loci (eQTL) analysis, and Mendelian Randomization(MR) analyses. Additionally, we used Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the functional roles and pathways of these genes. Finally, we validated the results obtained for the target genes.ResultsWe identified 486 highly expressed genes and 468 lowly expressed genes that play important roles in IPF. MR analysis identified six significantly co-expressed genes associated with IPF, specifically C12orf75, SPP1, ZG16B, LIN7A, PPP1R14A, and TLR2. These genes participate in essential biological processes and pathways, including macrophage activation and neural system regulation. Additionally, CIBERSORT analysis indicated a unique immune cell distribution in IPF, emphasized the significance of immunological processes in the disease. The MR analysis was consistent with the results of the analysis of variance in the validation cohort, which strengthens the reliability of our MR findings.ConclusionOur findings provide new insights into the molecular basis of IPF and highlight the promise of therapeutic interventions. They emphasize the potential of targeting specific molecular pathways for the treatment of IPF, laying the foundation for further research and clinical work. |
| first_indexed | 2024-04-24T22:40:49Z |
| format | Article |
| id | doaj.art-c7af0c0438eb45c2a4e07ad020b1b2f6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T22:40:49Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c7af0c0438eb45c2a4e07ad020b1b2f62024-03-19T04:38:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13751711375171Transcriptomics in idiopathic pulmonary fibrosis unveiled: a new perspective from differentially expressed genes to therapeutic targetsWenzhong Hu0Yun Xu1Guang’anmen Hospital South Campus, China Academy of Chinese Medical Sciences, Beijing, ChinaPeople's Hospital of Beijing Daxing District, Capital Medical University, Beijing, ChinaBackgroundThe underlying molecular pathways of idiopathic pulmonary fibrosis (IPF), a progressive lung condition with a high death rate, are still mostly unknown. By using microarray datasets, this study aims to identify new genetic targets for IPF and provide light on the genetic factors that contribute to the development of IPF.MethodWe conducted a comprehensive analysis of three independent IPF datasets from the Gene Expression Omnibus (GEO) database, employing R software for data handling and normalization. Our evaluation of the relationships between differentially expressed genes (DEGs) and IPF included differential expression analysis, expression quantitative trait loci (eQTL) analysis, and Mendelian Randomization(MR) analyses. Additionally, we used Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore the functional roles and pathways of these genes. Finally, we validated the results obtained for the target genes.ResultsWe identified 486 highly expressed genes and 468 lowly expressed genes that play important roles in IPF. MR analysis identified six significantly co-expressed genes associated with IPF, specifically C12orf75, SPP1, ZG16B, LIN7A, PPP1R14A, and TLR2. These genes participate in essential biological processes and pathways, including macrophage activation and neural system regulation. Additionally, CIBERSORT analysis indicated a unique immune cell distribution in IPF, emphasized the significance of immunological processes in the disease. The MR analysis was consistent with the results of the analysis of variance in the validation cohort, which strengthens the reliability of our MR findings.ConclusionOur findings provide new insights into the molecular basis of IPF and highlight the promise of therapeutic interventions. They emphasize the potential of targeting specific molecular pathways for the treatment of IPF, laying the foundation for further research and clinical work.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1375171/fullidiopathic pulmonary fibrosisdifferentially expressed genesmicroarray dataeQTL analysisMendelian randomizationimmune cell infiltration |
| spellingShingle | Wenzhong Hu Yun Xu Transcriptomics in idiopathic pulmonary fibrosis unveiled: a new perspective from differentially expressed genes to therapeutic targets Frontiers in Immunology idiopathic pulmonary fibrosis differentially expressed genes microarray data eQTL analysis Mendelian randomization immune cell infiltration |
| title | Transcriptomics in idiopathic pulmonary fibrosis unveiled: a new perspective from differentially expressed genes to therapeutic targets |
| title_full | Transcriptomics in idiopathic pulmonary fibrosis unveiled: a new perspective from differentially expressed genes to therapeutic targets |
| title_fullStr | Transcriptomics in idiopathic pulmonary fibrosis unveiled: a new perspective from differentially expressed genes to therapeutic targets |
| title_full_unstemmed | Transcriptomics in idiopathic pulmonary fibrosis unveiled: a new perspective from differentially expressed genes to therapeutic targets |
| title_short | Transcriptomics in idiopathic pulmonary fibrosis unveiled: a new perspective from differentially expressed genes to therapeutic targets |
| title_sort | transcriptomics in idiopathic pulmonary fibrosis unveiled a new perspective from differentially expressed genes to therapeutic targets |
| topic | idiopathic pulmonary fibrosis differentially expressed genes microarray data eQTL analysis Mendelian randomization immune cell infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1375171/full |
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