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Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension

BACKGROUND: The pathogenesis of pulmonary arterial hypertension (PAH) and associated biomarkers remain to be studied. Copper metabolism is an emerging metabolic research direction in many diseases, but its role in PAH is still unclear. METHODS: PAH-related datasets were downloaded from the Gene Expr...

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Autores principales: Wang, Lei, Zhang, Wei, Li, Cong, Chen, Xin, Huang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868507/
https://www.ncbi.nlm.nih.gov/pubmed/36690956
http://dx.doi.org/10.1186/s12890-023-02326-6
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author Wang, Lei
Zhang, Wei
Li, Cong
Chen, Xin
Huang, Jing
author_facet Wang, Lei
Zhang, Wei
Li, Cong
Chen, Xin
Huang, Jing
author_sort Wang, Lei
collection PubMed
description BACKGROUND: The pathogenesis of pulmonary arterial hypertension (PAH) and associated biomarkers remain to be studied. Copper metabolism is an emerging metabolic research direction in many diseases, but its role in PAH is still unclear. METHODS: PAH-related datasets were downloaded from the Gene Expression Omnibus database, and 2067 copper metabolism-related genes (CMGs) were obtained from the GeneCards database. Differential expression analysis and the Venn algorithm were used to acquire the differentially expressed CMGs (DE-CMGs). DE-CMGs were then used for the coexpression network construction to screen candidate key genes associated with PAH. Furthermore, the predictive performance of the model was verified by receiver operating characteristic (ROC) analysis, and genes with area under the curve (AUC) values greater than 0.8 were selected as diagnostic genes. Then support vector machine, least absolute shrinkage and selection operator regression, and Venn diagrams were applied to detect biomarkers. Moreover, gene set enrichment analysis was performed to explore the function of the biomarkers, and immune-related analyses were utilized to study the infiltration of immune cells. The drug-gene interaction database was used to predict potential therapeutic drugs for PAH using the biomarkers. Biomarkers expression in clinical samples was verified by real-time quantitative PCR. RESULTS: Four biomarkers (DDIT3, NFKBIA, OSM, and PTGER4) were screened. The ROC analysis showed that the 4 biomarkers performed well (AUCs > 0.7). The high expression groups for the 4 biomarkers were enriched in protein activity-related pathways including protein export, spliceosome and proteasome. Furthermore, 8 immune cell types were significantly different between the two groups, including naive B cells, memory B cells, and resting memory CD4 T cells. Afterward, a gene-drug network was constructed. This network illustrated that STREPTOZOCIN, IBUPROFEN, and CELECOXIB were shared by the PTGER4 and DDIT3. Finally, the results of RT-qPCR in clinical samples further confirmed the results of the public database for the expression of NFKBIA and OSM. CONCLUSION: In conclusion, four biomarkers (DDIT3, NFKBIA, OSM, and PTGER4) with considerable diagnostic values were identified, and a gene-drug network was further constructed. The results of this study may have significant implications for the development of new diagnostic biomarkers and actionable targets to expand treatment options for PAH patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-023-02326-6.
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spelling pubmed-98685072023-01-23 Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension Wang, Lei Zhang, Wei Li, Cong Chen, Xin Huang, Jing BMC Pulm Med Research BACKGROUND: The pathogenesis of pulmonary arterial hypertension (PAH) and associated biomarkers remain to be studied. Copper metabolism is an emerging metabolic research direction in many diseases, but its role in PAH is still unclear. METHODS: PAH-related datasets were downloaded from the Gene Expression Omnibus database, and 2067 copper metabolism-related genes (CMGs) were obtained from the GeneCards database. Differential expression analysis and the Venn algorithm were used to acquire the differentially expressed CMGs (DE-CMGs). DE-CMGs were then used for the coexpression network construction to screen candidate key genes associated with PAH. Furthermore, the predictive performance of the model was verified by receiver operating characteristic (ROC) analysis, and genes with area under the curve (AUC) values greater than 0.8 were selected as diagnostic genes. Then support vector machine, least absolute shrinkage and selection operator regression, and Venn diagrams were applied to detect biomarkers. Moreover, gene set enrichment analysis was performed to explore the function of the biomarkers, and immune-related analyses were utilized to study the infiltration of immune cells. The drug-gene interaction database was used to predict potential therapeutic drugs for PAH using the biomarkers. Biomarkers expression in clinical samples was verified by real-time quantitative PCR. RESULTS: Four biomarkers (DDIT3, NFKBIA, OSM, and PTGER4) were screened. The ROC analysis showed that the 4 biomarkers performed well (AUCs > 0.7). The high expression groups for the 4 biomarkers were enriched in protein activity-related pathways including protein export, spliceosome and proteasome. Furthermore, 8 immune cell types were significantly different between the two groups, including naive B cells, memory B cells, and resting memory CD4 T cells. Afterward, a gene-drug network was constructed. This network illustrated that STREPTOZOCIN, IBUPROFEN, and CELECOXIB were shared by the PTGER4 and DDIT3. Finally, the results of RT-qPCR in clinical samples further confirmed the results of the public database for the expression of NFKBIA and OSM. CONCLUSION: In conclusion, four biomarkers (DDIT3, NFKBIA, OSM, and PTGER4) with considerable diagnostic values were identified, and a gene-drug network was further constructed. The results of this study may have significant implications for the development of new diagnostic biomarkers and actionable targets to expand treatment options for PAH patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-023-02326-6. BioMed Central 2023-01-23 /pmc/articles/PMC9868507/ /pubmed/36690956 http://dx.doi.org/10.1186/s12890-023-02326-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wang, Lei
Zhang, Wei
Li, Cong
Chen, Xin
Huang, Jing
Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension
title Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension
title_full Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension
title_fullStr Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension
title_full_unstemmed Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension
title_short Identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension
title_sort identification of biomarkers related to copper metabolism in patients with pulmonary arterial hypertension
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868507/
https://www.ncbi.nlm.nih.gov/pubmed/36690956
http://dx.doi.org/10.1186/s12890-023-02326-6
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