Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD

Jiale Zhao,1,2,* Xiahui Ge,3,* Hailong Li,4,* Genfei Jing,5,* Weirong Ma,2 Yuchun Fan,2 Juan Chen,2,6 Zhijun Zhao,7,8 Jia Hou2,6 1School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Department of Pul...

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Main Authors: Zhao J, Ge X, Li H, Jing G, Ma W, Fan Y, Chen J, Zhao Z, Hou J
Format: Article
Language:English
Published: Dove Medical Press 2025-06-01
Series:International Journal of COPD
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Online Access:https://www.dovepress.com/hub-genes-prpf19-and-ppib-molecular-pathways-and-potential-biomarkers--peer-reviewed-fulltext-article-COPD
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author Zhao J
Ge X
Li H
Jing G
Ma W
Fan Y
Chen J
Zhao Z
Hou J
author_facet Zhao J
Ge X
Li H
Jing G
Ma W
Fan Y
Chen J
Zhao Z
Hou J
author_sort Zhao J
collection DOAJ
description Jiale Zhao,1,2,* Xiahui Ge,3,* Hailong Li,4,* Genfei Jing,5,* Weirong Ma,2 Yuchun Fan,2 Juan Chen,2,6 Zhijun Zhao,7,8 Jia Hou2,6 1School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China; 4Department of Respiratory Medicine, Ningxia Hospital of Integrated Traditional Chinese and Western Medicine, Yinchuan, Ningxia, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Yongning County People’s Hospital, Yinchuan, Ningxia, People’s Republic of China; 6Department of Key Laboratory of Ningxia Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 7Clinical Laboratory Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 8Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia Hou, Email houj@live.com Zhijun Zhao, Email z15815z@163.comBackground: Chronic Obstructive Pulmonary Disease (COPD), a complex respiratory disorder, results from genetic and environmental factors. Uncovering its genetic basis is vital for diagnostics and treatment. Robust genetic analysis is essential to establish a causal link.Methods: Genome-wide DNA methylation analysis was performed using the Illumina Infinium HumanMethylation850 BeadChip in peripheral blood from 8 COPD patients and 8 healthy smoking controls. Differentially methylated genes (DMGs) were cross-analyzed with differentially expressed genes (DEGs) identified from the Gene Expression Omnibus (GEO) dataset GSE38974 (23 COPD, 9 controls). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) networks were utilized to identify COPD-associated hub genes. Mendelian randomization (MR) analysis examined the causal relationship between hub genes and COPD. The expression of selected hub genes was validated through RT-qPCR (80 COPD, 62 controls), immunohistochemistry, and Western blot analyses (10 COPD and 10 controls).Results: We found 10,593 DMGs and 646 DEGs associated with COPD. These genes were compared with WGCNA module genes, and the Protein-Protein Interaction (PPI) network interaction diagram was drawn, thereby identifying five Hub genes: PPIB, HSPA2, PRPF19, FKBP10 and DOHH. The expression levels of DOHH, FKBP10, PPIB and PRPF19 are higher in COPD, while the expression level of HSPA2 is lower. MR results indicate a potential causal relationship between PRPF19, PPIB and COPD. RT-qPCR, immunohistochemistry and Western blot experiments verified that the expression of PRPF-19 and PPIB was up-regulated in peripheral blood and lung tissue, which was consistent with the results of bioinformatics analysis.Conclusion: Our findings suggest that PRPF19 and PPIB may serve as promising diagnostic biomarkers in COPD. Further studies are required to fully elucidate their roles in COPD pathogenesis.Keywords: chronic obstructive pulmonary disease, epigenetic susceptibility, hub genes, protein-protein interaction, Mendelian randomization
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spelling doaj-art-5dfd257dfd9a418fb748c1faa73714ad2025-08-20T03:32:33ZengDove Medical PressInternational Journal of COPD1178-20052025-06-01Volume 20Issue 118651880103805Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPDZhao J0Ge X1Li H2Jing G3Ma W4Fan YChen J5Zhao Z6Hou J7General Hospital of Ningxia Medical UniversityDepartment of Respiratory and Critical Care MedicineDepartment of Respiratory MedicineDepartment of Respiratory and Critical Care MedicineDepartment of Respiratory and Critical Care MedicineDepartment of Key Laboratory of Ningxia Stem Cell and Regenerative MedicineClinical Laboratory Center/Ningxia Key Laboratory of Clinical and Pathogenic MicrobiologyDepartment of Pulmonary and Critical Care MedicineJiale Zhao,1,2,* Xiahui Ge,3,* Hailong Li,4,* Genfei Jing,5,* Weirong Ma,2 Yuchun Fan,2 Juan Chen,2,6 Zhijun Zhao,7,8 Jia Hou2,6 1School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Shanghai Ninth People’s Hospital, Shanghai, People’s Republic of China; 4Department of Respiratory Medicine, Ningxia Hospital of Integrated Traditional Chinese and Western Medicine, Yinchuan, Ningxia, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Yongning County People’s Hospital, Yinchuan, Ningxia, People’s Republic of China; 6Department of Key Laboratory of Ningxia Stem Cell and Regenerative Medicine, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 7Clinical Laboratory Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 8Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia Hou, Email houj@live.com Zhijun Zhao, Email z15815z@163.comBackground: Chronic Obstructive Pulmonary Disease (COPD), a complex respiratory disorder, results from genetic and environmental factors. Uncovering its genetic basis is vital for diagnostics and treatment. Robust genetic analysis is essential to establish a causal link.Methods: Genome-wide DNA methylation analysis was performed using the Illumina Infinium HumanMethylation850 BeadChip in peripheral blood from 8 COPD patients and 8 healthy smoking controls. Differentially methylated genes (DMGs) were cross-analyzed with differentially expressed genes (DEGs) identified from the Gene Expression Omnibus (GEO) dataset GSE38974 (23 COPD, 9 controls). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) networks were utilized to identify COPD-associated hub genes. Mendelian randomization (MR) analysis examined the causal relationship between hub genes and COPD. The expression of selected hub genes was validated through RT-qPCR (80 COPD, 62 controls), immunohistochemistry, and Western blot analyses (10 COPD and 10 controls).Results: We found 10,593 DMGs and 646 DEGs associated with COPD. These genes were compared with WGCNA module genes, and the Protein-Protein Interaction (PPI) network interaction diagram was drawn, thereby identifying five Hub genes: PPIB, HSPA2, PRPF19, FKBP10 and DOHH. The expression levels of DOHH, FKBP10, PPIB and PRPF19 are higher in COPD, while the expression level of HSPA2 is lower. MR results indicate a potential causal relationship between PRPF19, PPIB and COPD. RT-qPCR, immunohistochemistry and Western blot experiments verified that the expression of PRPF-19 and PPIB was up-regulated in peripheral blood and lung tissue, which was consistent with the results of bioinformatics analysis.Conclusion: Our findings suggest that PRPF19 and PPIB may serve as promising diagnostic biomarkers in COPD. Further studies are required to fully elucidate their roles in COPD pathogenesis.Keywords: chronic obstructive pulmonary disease, epigenetic susceptibility, hub genes, protein-protein interaction, Mendelian randomizationhttps://www.dovepress.com/hub-genes-prpf19-and-ppib-molecular-pathways-and-potential-biomarkers--peer-reviewed-fulltext-article-COPDChronic obstructive pulmonary diseaseEpigenetic susceptibilityHub genesProtein-protein interactionMendelian randomization
spellingShingle Zhao J
Ge X
Li H
Jing G
Ma W
Fan Y
Chen J
Zhao Z
Hou J
Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD
International Journal of COPD
Chronic obstructive pulmonary disease
Epigenetic susceptibility
Hub genes
Protein-protein interaction
Mendelian randomization
title Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD
title_full Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD
title_fullStr Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD
title_full_unstemmed Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD
title_short Hub Genes PRPF19 and PPIB: Molecular Pathways and Potential Biomarkers in COPD
title_sort hub genes prpf19 and ppib molecular pathways and potential biomarkers in copd
topic Chronic obstructive pulmonary disease
Epigenetic susceptibility
Hub genes
Protein-protein interaction
Mendelian randomization
url https://www.dovepress.com/hub-genes-prpf19-and-ppib-molecular-pathways-and-potential-biomarkers--peer-reviewed-fulltext-article-COPD
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