Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma
Background: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma ce...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1159355/full |
| _version_ | 1797843808818298880 |
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| author | Bingxin Zhang Quanqiang Wang Tianyu Zhang Ziwei Zheng Zhili Lin Shujuan Zhou Dong Zheng Zixing Chen Sisi Zheng Yu Zhang Xuanru Lin Rujiao Dong Jingjing Chen Honglan Qian Xudong Hu Yan Zhuang Qianying Zhang Zhouxiang Jin Songfu Jiang Yongyong Ma Yongyong Ma Yongyong Ma |
| author_facet | Bingxin Zhang Quanqiang Wang Tianyu Zhang Ziwei Zheng Zhili Lin Shujuan Zhou Dong Zheng Zixing Chen Sisi Zheng Yu Zhang Xuanru Lin Rujiao Dong Jingjing Chen Honglan Qian Xudong Hu Yan Zhuang Qianying Zhang Zhouxiang Jin Songfu Jiang Yongyong Ma Yongyong Ma Yongyong Ma |
| author_sort | Bingxin Zhang |
| collection | DOAJ |
| description | Background: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma cells. In the development of MM, almost all patients undergo a relatively benign course from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM), which further progresses to active myeloma. However, the prognostic value of cuproptosis in MM remains unknown.Method: In this study, we systematically investigated the genetic variants, expression patterns, and prognostic value of cuproptosis-related genes (CRGs) in MM. CRG scores derived from the prognostic model were used to perform the risk stratification of MM patients. We then explored their differences in clinical characteristics and immune patterns and assessed their value in prognosis prediction and treatment response. Nomograms were also developed to improve predictive accuracy and clinical applicability. Finally, we collected MM cell lines and patient samples to validate marker gene expression by quantitative real-time PCR (qRT-PCR).Results: The evolution from MGUS and SMM to MM was also accompanied by differences in the CRG expression profile. Then, a well-performing cuproptosis-related risk model was developed to predict prognosis in MM and was validated in two external cohorts. The high-risk group exhibited higher clinical risk indicators. Cox regression analyses showed that the model was an independent prognostic predictor in MM. Patients in the high-risk group had significantly lower survival rates than those in the low-risk group (p < 0.001). Meanwhile, CRG scores were significantly correlated with immune infiltration, stemness index and immunotherapy sensitivity. We further revealed the close association between CRG scores and mitochondrial metabolism. Subsequently, the prediction nomogram showed good predictive power and calibration. Finally, the prognostic CRGs were further validated by qRT-PCR in vitro.Conclusion: CRGs were closely related to the immune pattern and self-renewal biology of cancer cells in MM. This prognostic model provided a new perspective for the risk stratification and treatment response prediction of MM patients. |
| first_indexed | 2024-04-09T17:11:57Z |
| format | Article |
| id | doaj.art-d77fb40a6a3f43dcb69d0962d35a3cca |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-09T17:11:57Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-d77fb40a6a3f43dcb69d0962d35a3cca2023-04-20T05:54:29ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-04-011110.3389/fcell.2023.11593551159355Identification and validation of a novel cuproptosis-related gene signature in multiple myelomaBingxin Zhang0Quanqiang Wang1Tianyu Zhang2Ziwei Zheng3Zhili Lin4Shujuan Zhou5Dong Zheng6Zixing Chen7Sisi Zheng8Yu Zhang9Xuanru Lin10Rujiao Dong11Jingjing Chen12Honglan Qian13Xudong Hu14Yan Zhuang15Qianying Zhang16Zhouxiang Jin17Songfu Jiang18Yongyong Ma19Yongyong Ma20Yongyong Ma21Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hepatobiliary Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaDepartment of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, ChinaKey Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, Wenzhou, Zhejiang, ChinaZhejiang Engineering Research Center for Hospital Emergency and Process Digitization, Wenzhou, Zhejiang, ChinaBackground: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma cells. In the development of MM, almost all patients undergo a relatively benign course from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM), which further progresses to active myeloma. However, the prognostic value of cuproptosis in MM remains unknown.Method: In this study, we systematically investigated the genetic variants, expression patterns, and prognostic value of cuproptosis-related genes (CRGs) in MM. CRG scores derived from the prognostic model were used to perform the risk stratification of MM patients. We then explored their differences in clinical characteristics and immune patterns and assessed their value in prognosis prediction and treatment response. Nomograms were also developed to improve predictive accuracy and clinical applicability. Finally, we collected MM cell lines and patient samples to validate marker gene expression by quantitative real-time PCR (qRT-PCR).Results: The evolution from MGUS and SMM to MM was also accompanied by differences in the CRG expression profile. Then, a well-performing cuproptosis-related risk model was developed to predict prognosis in MM and was validated in two external cohorts. The high-risk group exhibited higher clinical risk indicators. Cox regression analyses showed that the model was an independent prognostic predictor in MM. Patients in the high-risk group had significantly lower survival rates than those in the low-risk group (p < 0.001). Meanwhile, CRG scores were significantly correlated with immune infiltration, stemness index and immunotherapy sensitivity. We further revealed the close association between CRG scores and mitochondrial metabolism. Subsequently, the prediction nomogram showed good predictive power and calibration. Finally, the prognostic CRGs were further validated by qRT-PCR in vitro.Conclusion: CRGs were closely related to the immune pattern and self-renewal biology of cancer cells in MM. This prognostic model provided a new perspective for the risk stratification and treatment response prediction of MM patients.https://www.frontiersin.org/articles/10.3389/fcell.2023.1159355/fullmultiple myelomacuproptosisprognostic gene signaturetumor microenvironmenttricarboxylic acid cycle |
| spellingShingle | Bingxin Zhang Quanqiang Wang Tianyu Zhang Ziwei Zheng Zhili Lin Shujuan Zhou Dong Zheng Zixing Chen Sisi Zheng Yu Zhang Xuanru Lin Rujiao Dong Jingjing Chen Honglan Qian Xudong Hu Yan Zhuang Qianying Zhang Zhouxiang Jin Songfu Jiang Yongyong Ma Yongyong Ma Yongyong Ma Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma Frontiers in Cell and Developmental Biology multiple myeloma cuproptosis prognostic gene signature tumor microenvironment tricarboxylic acid cycle |
| title | Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma |
| title_full | Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma |
| title_fullStr | Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma |
| title_full_unstemmed | Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma |
| title_short | Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma |
| title_sort | identification and validation of a novel cuproptosis related gene signature in multiple myeloma |
| topic | multiple myeloma cuproptosis prognostic gene signature tumor microenvironment tricarboxylic acid cycle |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1159355/full |
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