Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma
Abstract Esophageal carcinoma (ESCA) is a common type of cancer with high mortality. Cuproptosis is a new type of cell death and is characterized by the dependence on mitochondrial respiration and protein lipoylation. However, the potential roles of cuproptosis-related genes (CRGs) in ESCA remain el...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01164-5 |
| _version_ | 1811281954309406720 |
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| author | Runmin Jiang Yu Huan Yan Li Xinyue Gao Qiang Sun Feng Zhang Tao Jiang |
| author_facet | Runmin Jiang Yu Huan Yan Li Xinyue Gao Qiang Sun Feng Zhang Tao Jiang |
| author_sort | Runmin Jiang |
| collection | DOAJ |
| description | Abstract Esophageal carcinoma (ESCA) is a common type of cancer with high mortality. Cuproptosis is a new type of cell death and is characterized by the dependence on mitochondrial respiration and protein lipoylation. However, the potential roles of cuproptosis-related genes (CRGs) in ESCA remain elusive. Here, we systematically assessed the transcriptional and genetic alterations of CRGs in ESCA. We identified a CRGs signature for ESCA patients. A 6-CRGs signature was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis along with the univariate cox regression analysis and differential genes analysis. The CRGs score could significantly stratify ESCA patients’ survival and a high CRGs score was significantly correlated with worse overall survival. Moreover, higher CRGs score indicated higher pathology grades and aberrant cell adhesion, possibly via the PI3K-AKT pathway, which could also underly their increased sensitivity to PI3K-AKT pathway inhibitors. In addition, patients with high CRGs tend to hold more mutation load and abnormal APOBEC mutation. Notably, a higher CRGs score was anomalously associated with more immune infiltration, which could explain its malignancy by increased PD-L1 stability and a higher proportion of bystander T cells. In conclusion, our report revealed the significance of cuproptosis in ESCA and may have therapeutic potential in activating the bystander T cells. |
| first_indexed | 2024-04-13T01:42:53Z |
| format | Article |
| id | doaj.art-40e671dcbf1e4729b1869a299898ed0f |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-04-13T01:42:53Z |
| publishDate | 2022-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-40e671dcbf1e4729b1869a299898ed0f2022-12-22T03:08:08ZengNature Publishing GroupCell Death Discovery2058-77162022-08-018111310.1038/s41420-022-01164-5Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinomaRunmin Jiang0Yu Huan1Yan Li2Xinyue Gao3Qiang Sun4Feng Zhang5Tao Jiang6Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical UniversityDepartment of Neurosurgery, Xijing Hospital, The Fourth Military Medical UniversityDepartment of Radiation Oncology, Xijing Hospital, The Fourth Military Medical UniversityLaboratory of Cell Engineering, Institute of Biotechnology; Research Unit of Cell Death Mechanism, 2021RU008, Chinese Academy of Medical ScienceLaboratory of Cell Engineering, Institute of Biotechnology; Research Unit of Cell Death Mechanism, 2021RU008, Chinese Academy of Medical ScienceState Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, The Fourth Military Medical UniversityDepartment of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical UniversityAbstract Esophageal carcinoma (ESCA) is a common type of cancer with high mortality. Cuproptosis is a new type of cell death and is characterized by the dependence on mitochondrial respiration and protein lipoylation. However, the potential roles of cuproptosis-related genes (CRGs) in ESCA remain elusive. Here, we systematically assessed the transcriptional and genetic alterations of CRGs in ESCA. We identified a CRGs signature for ESCA patients. A 6-CRGs signature was constructed by the least absolute shrinkage and selection operator (LASSO) regression analysis along with the univariate cox regression analysis and differential genes analysis. The CRGs score could significantly stratify ESCA patients’ survival and a high CRGs score was significantly correlated with worse overall survival. Moreover, higher CRGs score indicated higher pathology grades and aberrant cell adhesion, possibly via the PI3K-AKT pathway, which could also underly their increased sensitivity to PI3K-AKT pathway inhibitors. In addition, patients with high CRGs tend to hold more mutation load and abnormal APOBEC mutation. Notably, a higher CRGs score was anomalously associated with more immune infiltration, which could explain its malignancy by increased PD-L1 stability and a higher proportion of bystander T cells. In conclusion, our report revealed the significance of cuproptosis in ESCA and may have therapeutic potential in activating the bystander T cells.https://doi.org/10.1038/s41420-022-01164-5 |
| spellingShingle | Runmin Jiang Yu Huan Yan Li Xinyue Gao Qiang Sun Feng Zhang Tao Jiang Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma Cell Death Discovery |
| title | Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma |
| title_full | Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma |
| title_fullStr | Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma |
| title_full_unstemmed | Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma |
| title_short | Transcriptional and genetic alterations of cuproptosis-related genes correlated to malignancy and immune-infiltrate of esophageal carcinoma |
| title_sort | transcriptional and genetic alterations of cuproptosis related genes correlated to malignancy and immune infiltrate of esophageal carcinoma |
| url | https://doi.org/10.1038/s41420-022-01164-5 |
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