Transcriptomic Characterization of Copper-Binding Proteins for Predicting Prognosis in Glioma
Background: Copper and copper-binding proteins are key components of tumor progression as they play important roles in tumor invasion and migration, but their associations in gliomas remain unclear. Methods: Transcriptomic datasets of glioblastoma, low-grade glioma, and normal brain cortex were deri...
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| Format: | Article |
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MDPI AG
2023-10-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/10/1460 |
| _version_ | 1797574526661296128 |
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| author | Hao-Long Zeng Huijun Li Qing Yang Chao-Xi Li |
| author_facet | Hao-Long Zeng Huijun Li Qing Yang Chao-Xi Li |
| author_sort | Hao-Long Zeng |
| collection | DOAJ |
| description | Background: Copper and copper-binding proteins are key components of tumor progression as they play important roles in tumor invasion and migration, but their associations in gliomas remain unclear. Methods: Transcriptomic datasets of glioblastoma, low-grade glioma, and normal brain cortex were derived from the TCGA and GTEX databases. Differentially expressed genes (DEGs) of copper-binding proteins were screened and used to construct a prognostic model based on COX and LASSO regression, which was further validated by the CGGA datasets. The expressions of risk-model genes were selectively confirmed via anatomic feature-based expression analysis and immunohistochemistry. The risk score was stratified by age, gender, WHO grade, IDH1 mutation, MGMT promoter methylation, and 1p/19q codeletion status, and a nomogram was constructed and validated. Results: A total of 21 DEGs of copper-binding proteins were identified and a six-gene risk-score model was constructed, consisting of ANG, F5, IL1A, LOXL1, LOXL2, and STEAP3, which accurately predicted 1-, 3-, and 5-year overall survival rates, with the AUC values of 0.87, 0.88, and 0.82, respectively. The high-risk group had a significantly shorter OS (<i>p</i> < 0.0001) and was associated with old age, wild-type IDH1, a high WHO grade, an unmethylated MGMT promoter, and 1p/19q non-codeletion and had higher levels of immune cell infiltration, cancer-immunity suppressor, and immune checkpoint gene expression as well as a higher TMB. Conclusions: The model based on the genes of copper-binding proteins could contribute to prognosis prediction and provide potential targets against gliomas. |
| first_indexed | 2024-03-10T21:23:44Z |
| format | Article |
| id | doaj.art-a12de7fe00aa4d8daffa75f0bafd444b |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T21:23:44Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-a12de7fe00aa4d8daffa75f0bafd444b2023-11-19T15:53:15ZengMDPI AGBrain Sciences2076-34252023-10-011310146010.3390/brainsci13101460Transcriptomic Characterization of Copper-Binding Proteins for Predicting Prognosis in GliomaHao-Long Zeng0Huijun Li1Qing Yang2Chao-Xi Li3Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaInstitute of Food Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, ChinaDepartment of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaBackground: Copper and copper-binding proteins are key components of tumor progression as they play important roles in tumor invasion and migration, but their associations in gliomas remain unclear. Methods: Transcriptomic datasets of glioblastoma, low-grade glioma, and normal brain cortex were derived from the TCGA and GTEX databases. Differentially expressed genes (DEGs) of copper-binding proteins were screened and used to construct a prognostic model based on COX and LASSO regression, which was further validated by the CGGA datasets. The expressions of risk-model genes were selectively confirmed via anatomic feature-based expression analysis and immunohistochemistry. The risk score was stratified by age, gender, WHO grade, IDH1 mutation, MGMT promoter methylation, and 1p/19q codeletion status, and a nomogram was constructed and validated. Results: A total of 21 DEGs of copper-binding proteins were identified and a six-gene risk-score model was constructed, consisting of ANG, F5, IL1A, LOXL1, LOXL2, and STEAP3, which accurately predicted 1-, 3-, and 5-year overall survival rates, with the AUC values of 0.87, 0.88, and 0.82, respectively. The high-risk group had a significantly shorter OS (<i>p</i> < 0.0001) and was associated with old age, wild-type IDH1, a high WHO grade, an unmethylated MGMT promoter, and 1p/19q non-codeletion and had higher levels of immune cell infiltration, cancer-immunity suppressor, and immune checkpoint gene expression as well as a higher TMB. Conclusions: The model based on the genes of copper-binding proteins could contribute to prognosis prediction and provide potential targets against gliomas.https://www.mdpi.com/2076-3425/13/10/1460copper bindinggliomaprognosisbioinformaticsrisk model |
| spellingShingle | Hao-Long Zeng Huijun Li Qing Yang Chao-Xi Li Transcriptomic Characterization of Copper-Binding Proteins for Predicting Prognosis in Glioma Brain Sciences copper binding glioma prognosis bioinformatics risk model |
| title | Transcriptomic Characterization of Copper-Binding Proteins for Predicting Prognosis in Glioma |
| title_full | Transcriptomic Characterization of Copper-Binding Proteins for Predicting Prognosis in Glioma |
| title_fullStr | Transcriptomic Characterization of Copper-Binding Proteins for Predicting Prognosis in Glioma |
| title_full_unstemmed | Transcriptomic Characterization of Copper-Binding Proteins for Predicting Prognosis in Glioma |
| title_short | Transcriptomic Characterization of Copper-Binding Proteins for Predicting Prognosis in Glioma |
| title_sort | transcriptomic characterization of copper binding proteins for predicting prognosis in glioma |
| topic | copper binding glioma prognosis bioinformatics risk model |
| url | https://www.mdpi.com/2076-3425/13/10/1460 |
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