Identification and immunological role of cuproptosis in osteoporosis
Background: osteoporosis is a skeletal disorder disease features low bone mass and poor bone architecture, which predisposes to increased risk of fracture. Copper death is a newly recognized form of cell death caused by excess copper ions, which presumably involve in various disease. Accordingly, we...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024027907 |
| _version_ | 1797259891282280448 |
|---|---|
| author | Tongying Chen Zhijie Gao Yuedong Wang Jiachun Huang Shuhua Liu Yanping Lin Sai Fu Lei Wan Ying Li Hongxing Huang Zhihai Zhang |
| author_facet | Tongying Chen Zhijie Gao Yuedong Wang Jiachun Huang Shuhua Liu Yanping Lin Sai Fu Lei Wan Ying Li Hongxing Huang Zhihai Zhang |
| author_sort | Tongying Chen |
| collection | DOAJ |
| description | Background: osteoporosis is a skeletal disorder disease features low bone mass and poor bone architecture, which predisposes to increased risk of fracture. Copper death is a newly recognized form of cell death caused by excess copper ions, which presumably involve in various disease. Accordingly, we intended to investigate the molecular clusters related to the cuproptosis in osteoporosis and to construct a predictive model. Methods: we investigated the expression patterns of cuproptosis regulators and immune signatures in osteoporosis based on the GSE56815 dataset. Through analysis of 40 osteoporosis samples, we investigated molecular clustering on the basis of cuproptosis--related genes, together with the associated immune cell infiltration. The WGCNA algorithm was applied to detect cluster-specific differentially expressed genes. Afterwards, the optimum machine model was selected by calculating the performance of the support vector machine model, random forest model, eXtreme Gradient Boosting and generalized linear model. Nomogram, decision curve analysis, calibration curves, and the GSE7158 dataset was utilizing to confirm the prediction efficiency. Results: Differences between osteoporotic and non-osteoporotic controls confirm poorly adjusted copper death-related genes and triggered immune responses. In osteoporosis, two clusters of molecules in connection with copper death proliferation were outlined. The assessed levels of immune infiltration showed prominent heterogeneity between the different clusters. Cluster 2 was characterized by a raised immune score accompanied with relatively high levels of immune infiltration. The functional analysis we performed showed a close relationship between the different immune responses and specific differentially expressed genes in cluster 2. The random forest machine model showed the optimum discriminatory performance due to relatively low residuals and root mean square errors. Finally, a random forest model based on 5 genes was built, showing acceptable performance in an external validation dataset (AUC = 0.750). Calibration curve, Nomogram, and decision curve analyses also evinced fidelity in predicting subtypes of osteoporosis. Conclusion: Our study identifies the role of cuproptosis in OP and essentially illustrates the underlying molecular mechanisms that lead to OP heterogeneity. |
| first_indexed | 2024-03-07T18:36:35Z |
| format | Article |
| id | doaj.art-d19e5937dedb4ca8814cf172ca066fdf |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T23:16:38Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-d19e5937dedb4ca8814cf172ca066fdf2024-03-17T07:56:11ZengElsevierHeliyon2405-84402024-03-01105e26759Identification and immunological role of cuproptosis in osteoporosisTongying Chen0Zhijie Gao1Yuedong Wang2Jiachun Huang3Shuhua Liu4Yanping Lin5Sai Fu6Lei Wan7Ying Li8Hongxing Huang9Zhihai Zhang10Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Second Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaThe First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaGuangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Laboratory Affiliated to National Key Discipline of Orthopaedic and Traumatology of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, ChinaThe Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Qifu Hospital Affiliated to Jinan University, Guangzhou, ChinaThe Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Laboratory Affiliated to National Key Discipline of Orthopaedic and Traumatology of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Corresponding author. The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Laboratory Affiliated to National Key Discipline of Orthopaedic and Traumatology of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Corresponding author. 261 Longxi Rd., Guangzhou, Guangdong, 510360, China.Background: osteoporosis is a skeletal disorder disease features low bone mass and poor bone architecture, which predisposes to increased risk of fracture. Copper death is a newly recognized form of cell death caused by excess copper ions, which presumably involve in various disease. Accordingly, we intended to investigate the molecular clusters related to the cuproptosis in osteoporosis and to construct a predictive model. Methods: we investigated the expression patterns of cuproptosis regulators and immune signatures in osteoporosis based on the GSE56815 dataset. Through analysis of 40 osteoporosis samples, we investigated molecular clustering on the basis of cuproptosis--related genes, together with the associated immune cell infiltration. The WGCNA algorithm was applied to detect cluster-specific differentially expressed genes. Afterwards, the optimum machine model was selected by calculating the performance of the support vector machine model, random forest model, eXtreme Gradient Boosting and generalized linear model. Nomogram, decision curve analysis, calibration curves, and the GSE7158 dataset was utilizing to confirm the prediction efficiency. Results: Differences between osteoporotic and non-osteoporotic controls confirm poorly adjusted copper death-related genes and triggered immune responses. In osteoporosis, two clusters of molecules in connection with copper death proliferation were outlined. The assessed levels of immune infiltration showed prominent heterogeneity between the different clusters. Cluster 2 was characterized by a raised immune score accompanied with relatively high levels of immune infiltration. The functional analysis we performed showed a close relationship between the different immune responses and specific differentially expressed genes in cluster 2. The random forest machine model showed the optimum discriminatory performance due to relatively low residuals and root mean square errors. Finally, a random forest model based on 5 genes was built, showing acceptable performance in an external validation dataset (AUC = 0.750). Calibration curve, Nomogram, and decision curve analyses also evinced fidelity in predicting subtypes of osteoporosis. Conclusion: Our study identifies the role of cuproptosis in OP and essentially illustrates the underlying molecular mechanisms that lead to OP heterogeneity.http://www.sciencedirect.com/science/article/pii/S2405844024027907OsteoporosisCuproptosisImmune infiltrationMitochondria |
| spellingShingle | Tongying Chen Zhijie Gao Yuedong Wang Jiachun Huang Shuhua Liu Yanping Lin Sai Fu Lei Wan Ying Li Hongxing Huang Zhihai Zhang Identification and immunological role of cuproptosis in osteoporosis Heliyon Osteoporosis Cuproptosis Immune infiltration Mitochondria |
| title | Identification and immunological role of cuproptosis in osteoporosis |
| title_full | Identification and immunological role of cuproptosis in osteoporosis |
| title_fullStr | Identification and immunological role of cuproptosis in osteoporosis |
| title_full_unstemmed | Identification and immunological role of cuproptosis in osteoporosis |
| title_short | Identification and immunological role of cuproptosis in osteoporosis |
| title_sort | identification and immunological role of cuproptosis in osteoporosis |
| topic | Osteoporosis Cuproptosis Immune infiltration Mitochondria |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024027907 |
| work_keys_str_mv | AT tongyingchen identificationandimmunologicalroleofcuproptosisinosteoporosis AT zhijiegao identificationandimmunologicalroleofcuproptosisinosteoporosis AT yuedongwang identificationandimmunologicalroleofcuproptosisinosteoporosis AT jiachunhuang identificationandimmunologicalroleofcuproptosisinosteoporosis AT shuhualiu identificationandimmunologicalroleofcuproptosisinosteoporosis AT yanpinglin identificationandimmunologicalroleofcuproptosisinosteoporosis AT saifu identificationandimmunologicalroleofcuproptosisinosteoporosis AT leiwan identificationandimmunologicalroleofcuproptosisinosteoporosis AT yingli identificationandimmunologicalroleofcuproptosisinosteoporosis AT hongxinghuang identificationandimmunologicalroleofcuproptosisinosteoporosis AT zhihaizhang identificationandimmunologicalroleofcuproptosisinosteoporosis |