Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury
Background: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recen...
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1269478/full |
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| author | Jianying Qin Jianying Qin Jianying Qin Xiaoyue Xiao Silin Li Silin Li Silin Li Ning Wen Ning Wen Ning Wen Ke Qin Ke Qin Ke Qin Haibin Li Haibin Li Haibin Li Jihua Wu Jihua Wu Jihua Wu Bing Lu Bing Lu Bing Lu Minghu Li Minghu Li Minghu Li Xuyong Sun Xuyong Sun Xuyong Sun |
| author_facet | Jianying Qin Jianying Qin Jianying Qin Xiaoyue Xiao Silin Li Silin Li Silin Li Ning Wen Ning Wen Ning Wen Ke Qin Ke Qin Ke Qin Haibin Li Haibin Li Haibin Li Jihua Wu Jihua Wu Jihua Wu Bing Lu Bing Lu Bing Lu Minghu Li Minghu Li Minghu Li Xuyong Sun Xuyong Sun Xuyong Sun |
| author_sort | Jianying Qin |
| collection | DOAJ |
| description | Background: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recently discovered form of programmed cell death. To date, no studies have been conducted on the mechanisms by which cuproptosis-related genes (CRGs) regulate ALIRI. Therefore, we explored the potential biomarkers related to cuproptosis to provide new insights into the treatment of ALIRI.Materials and methods: Datasets containing pre- and post-LTx lung biopsy samples and CRGs were obtained from the GEO database and previous studies. We identified differentially expressed CRGs (DE-CRGs) and performed functional analyses. Biomarker genes were selected using three machine learning algorithms. The ROC curve and logistic regression model (LRM) of these biomarkers were constructed. CIBERSORT was used to calculate the number of infiltrating immune cells pre- and post-LTx, and the correlation between these biomarkers and immune cells was analyzed. A competing endogenous RNA network was constructed using these biomarkers. Finally, the biomarkers were verified in a validation set and a rat LTx model using qRT-PCR and Western blotting.Results: Fifteen DE-CRGs were identified. GO analysis revealed that DE-CRGs were significantly enriched in the mitochondrial acetyl-CoA biosynthetic process from pyruvate, protein lipoylation, the tricarboxylic acid (TCA) cycle, and copper-transporting ATPase activity. KEGG enrichment analysis showed that the DE-CRGs were mainly enriched in metabolic pathways, carbon metabolism, and the TCA cycle. NFE2L2, NLRP3, LIPT1, and MTF1 were identified as potential biomarker genes. The AUC of the ROC curve for each biomarker was greater than 0.8, and the LRM provided an excellent classifier with an AUC of 0.96. These biomarkers were validated in another dataset and a rat LTx model, which exhibited good performance. In the CIBERSORT analysis, differentially expressed immune cells were identified, and the biomarkers were associated with the immune cells.Conclusion:NFE2L2, NLRP3, LIPT1, and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of cuproptosis in ALIRI. |
| first_indexed | 2024-03-10T00:05:22Z |
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| language | English |
| last_indexed | 2024-03-10T00:05:22Z |
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| spelling | doaj.art-8225ed140ca447e7b36548221a0f868b2023-11-23T16:08:40ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-11-011010.3389/fmolb.2023.12694781269478Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injuryJianying Qin0Jianying Qin1Jianying Qin2Xiaoyue Xiao3Silin Li4Silin Li5Silin Li6Ning Wen7Ning Wen8Ning Wen9Ke Qin10Ke Qin11Ke Qin12Haibin Li13Haibin Li14Haibin Li15Jihua Wu16Jihua Wu17Jihua Wu18Bing Lu19Bing Lu20Bing Lu21Minghu Li22Minghu Li23Minghu Li24Xuyong Sun25Xuyong Sun26Xuyong Sun27Transplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaDepartment of Pathology, The Fifth Affiliated Hospital of Guangxi Medical University, The First People’s Hospital of Nanning, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaTransplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, ChinaGuangxi Clinical Research Center for Organ Transplantation, Nanning, ChinaGuangxi Key Laboratory of Organ Donation and Transplantation, Nanning, ChinaBackground: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recently discovered form of programmed cell death. To date, no studies have been conducted on the mechanisms by which cuproptosis-related genes (CRGs) regulate ALIRI. Therefore, we explored the potential biomarkers related to cuproptosis to provide new insights into the treatment of ALIRI.Materials and methods: Datasets containing pre- and post-LTx lung biopsy samples and CRGs were obtained from the GEO database and previous studies. We identified differentially expressed CRGs (DE-CRGs) and performed functional analyses. Biomarker genes were selected using three machine learning algorithms. The ROC curve and logistic regression model (LRM) of these biomarkers were constructed. CIBERSORT was used to calculate the number of infiltrating immune cells pre- and post-LTx, and the correlation between these biomarkers and immune cells was analyzed. A competing endogenous RNA network was constructed using these biomarkers. Finally, the biomarkers were verified in a validation set and a rat LTx model using qRT-PCR and Western blotting.Results: Fifteen DE-CRGs were identified. GO analysis revealed that DE-CRGs were significantly enriched in the mitochondrial acetyl-CoA biosynthetic process from pyruvate, protein lipoylation, the tricarboxylic acid (TCA) cycle, and copper-transporting ATPase activity. KEGG enrichment analysis showed that the DE-CRGs were mainly enriched in metabolic pathways, carbon metabolism, and the TCA cycle. NFE2L2, NLRP3, LIPT1, and MTF1 were identified as potential biomarker genes. The AUC of the ROC curve for each biomarker was greater than 0.8, and the LRM provided an excellent classifier with an AUC of 0.96. These biomarkers were validated in another dataset and a rat LTx model, which exhibited good performance. In the CIBERSORT analysis, differentially expressed immune cells were identified, and the biomarkers were associated with the immune cells.Conclusion:NFE2L2, NLRP3, LIPT1, and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of cuproptosis in ALIRI.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1269478/fullcuproptosisischemia-reperfusion injuryallograft lungbiomarkersimmune infiltration |
| spellingShingle | Jianying Qin Jianying Qin Jianying Qin Xiaoyue Xiao Silin Li Silin Li Silin Li Ning Wen Ning Wen Ning Wen Ke Qin Ke Qin Ke Qin Haibin Li Haibin Li Haibin Li Jihua Wu Jihua Wu Jihua Wu Bing Lu Bing Lu Bing Lu Minghu Li Minghu Li Minghu Li Xuyong Sun Xuyong Sun Xuyong Sun Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury Frontiers in Molecular Biosciences cuproptosis ischemia-reperfusion injury allograft lung biomarkers immune infiltration |
| title | Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury |
| title_full | Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury |
| title_fullStr | Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury |
| title_full_unstemmed | Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury |
| title_short | Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury |
| title_sort | identification of cuproptosis related biomarkers and analysis of immune infiltration in allograft lung ischemia reperfusion injury |
| topic | cuproptosis ischemia-reperfusion injury allograft lung biomarkers immune infiltration |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1269478/full |
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