Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma

doi:10.3389/fcell.2023.1159355

科研成果详情

题名	Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma
作者	Zhang, Bingxin1; Wang, Quanqiang1; Zhang, Tianyu1; Zheng, Ziwei1; Lin, Zhili1; Zhou, Shujuan1; Zheng, Dong 1; Chen, Zixing2; Zheng, Sisi 1; Zhang, Yu 1; Lin, Xuanru1; Dong, Rujiao1; Chen, Jingjing1; Qian, Honglan1; Hu, Xudong1; Zhuang, Yan1; Zhang, Qianying 1; Jin, Zhouxiang2; Jiang, Songfu1; Ma, Yongyong1,3,4
发表日期	2023-04-20
发表期刊	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	multiple myeloma cuproptosis prognostic gene signature tumor microenvironment tricarboxylic acid cycle
其他关键词	INTERNATIONAL STAGING SYSTEM ; DISULFIRAM TARGETS CANCER ; CELL-DEATH ; BORTEZOMIB-RESISTANCE ; GLUTAMINE-METABOLISM ; AEROBIC GLYCOLYSIS ; OXIDATIVE STRESS ; EXPRESSION ; COPPER ; PROGRESSION
摘要	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.
资助项目	National Natural Science Foundation[82270212];Natural Science Foundation of Zhejiang province[LY20H080003];Wenzhou Municipal Science and Technology Bureau[Y20220716];
出版者	FRONTIERS MEDIA SA
ISSN	2296-634X
卷号	11
DOI	10.3389/fcell.2023.1159355
页数	23
WOS类目	Cell Biology ; Developmental Biology
WOS研究方向	Cell Biology ; Developmental Biology
WOS记录号	WOS:000981099700001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	37152283
SCOPUSEID	2-s2.0-85157996751
通讯作者地址	[Jiang, Songfu]Department of Hematology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Ma, Yongyong]Department of Hematology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China ; [Jin, Zhouxiang]Department of Hepatobiliary Surgery,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China
Scopus学科分类	Developmental Biology;Cell Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180125
专题	附属第一医院第二临床医学院、附属第二医院、育英儿童医院
通讯作者	Jin, Zhouxiang; Jiang, Songfu; Ma, Yongyong
作者单位	1.Department of Hematology,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 2.Department of Hepatobiliary Surgery,The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,China; 3.Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province,Zhejiang,Wenzhou,China; 4.Zhejiang Engineering Research Center for Hospital Emergency and Process Digitization,Zhejiang,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 第二临床医学院，附属第二医院、育英儿童医院; 附属第二医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Zhang, Bingxin,Wang, Quanqiang,Zhang, Tianyu,et al. Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2023,11.
APA	Zhang, Bingxin., Wang, Quanqiang., Zhang, Tianyu., Zheng, Ziwei., Lin, Zhili., ... & Ma, Yongyong. (2023). Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 11.
MLA	Zhang, Bingxin,et al."Identification and validation of a novel cuproptosis-related gene signature in multiple myeloma".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 11(2023).