Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma

doi:10.34133/research.0036

科研成果详情

题名	Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma
作者	Qi, Feng 1; Li, Jia 2; Qi, Zhuoran 2; Zhang, Jian 2; Zhou, Bin 3; Yang, Biwei 2; Qin, Wenxing 4; Cui, Wenguo 1,5; Xia, Jinglin2,6
发表日期	2023-01-13
发表期刊	Research 影响因子和分区
语种	英语
原始文献类型	Journal article (JA) ; Article
关键词	Amino acids Cell death Diagnosis Genes Amino acid metabolism Carcinoma patients Comprehensive metabolic profiling Dynamic network Genome wide analysis Hepatocellular carcinoma Immune cells Metabolic characteristics Metabolic dysregulation Therapeutic modality
其他关键词	SIGNALING PATHWAYS ; CANCER ; CELLS ; KYNURENINE
摘要	Understanding the details of metabolic reprogramming in hepatocellular carcinoma (HCC) is critical to improve stratification for therapy. Both multiomics analysis and cross-cohort validation were performed to investigate the metabolic dysregulation of 562 HCC patients from 4 cohorts. On the basis of the identified dynamic network biomarkers, 227 substantial metabolic genes were identified and a total of 343 HCC patients were classified into 4 heterogeneous metabolic clusters with distinct metabolic characteristics: cluster 1, the pyruvate subtype, associated with upregulated pyruvate metabolism; cluster 2, the amino acid subtype, with dysregulated amino acid metabolism as the reference; cluster 3, the mixed subtype, in which lipid metabolism, amino acid metabolism, and glycan metabolism are dysregulated; and cluster 4, the glycolytic subtype, associated with the dysregulated carbohydrate metabolism. These 4 clusters showed distinct prognoses, clinical characteristics and immune cell infiltrations, which was further validated by genomic alterations, transcriptomics, metabolomics, and immune cell profiles in the other 3 independent cohorts. Besides, the sensitivity of different clusters to metabolic inhibitors varied depending on their metabolic features. Importantly, cluster 2 is rich in immune cells in tumor tissues, especially programmed cell death protein 1 (PD-1)-expressing cells, which may be due to the tryptophan metabolism disorders, and potentially benefiting more from PD-1 treatment. In conclusion, our results suggest the metabolic heterogeneity of HCC and make it possible to treat HCC patients precisely and effectively on specific metabolic characteristics. © 2023 Feng Qi et al.
资助项目	Natural Science Foundation of China[81871920,81972233,82202874];
出版者	American Association for the Advancement of Science
ISSN	2096-5168
EISSN	2639-5274
卷号	6
DOI	10.34133/research.0036
页数	17
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000995897900001
收录类别	EI ; SCIE ; SCOPUS ; PUBMED
EI入藏号	20231513882286
EI主题词	Metabolism
EI分类号	461.2 Biological Materials and Tissue Engineering ; 461.6 Medicine and Pharmacology ; 461.9 Biology ; 804.1 Organic Compounds
URL	查看原文
Pubmed记录号	3704051
Scopus记录号	2-s2.0-85152139080
通讯作者地址	[Qin, Wenxing]Phase I Clinical Trial Center,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,No. 270, Dong’an Road,Shanghai,200032,China ; [Cui, Wenguo]Department of Oncology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200000,China ; [Xia, Jinglin]National Medical Center,National Clinical Research Center for Interventional Medicine,Liver Cancer Institute,Zhongshan Hospital,Fudan University,180 Fenglin Road,Shanghai,200032,China
scopus学科分类	Multidisciplinary
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/174984
专题	第一临床医学院（信息与工程学院）、附属第一医院_浙江省胰脏肝脏危重性疾病重点实验室附属第一医院
通讯作者	Qin, Wenxing; Cui, Wenguo; Xia, Jinglin
作者单位	1.Department of Oncology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200000,China; 2.National Medical Center,National Clinical Research Center for Interventional Medicine,Liver Cancer Institute,Zhongshan Hospital,Fudan University,180 Fenglin Road,Shanghai,200032,China; 3.Department of Hepatic Surgery VI,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University,Shanghai,200433,China; 4.Phase I Clinical Trial Center,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,No. 270, Dong’an Road,Shanghai,200032,China; 5.Department of Orthopaedics,Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases,Shanghai Institute of Traumatology and Orthopaedics,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,200000,China; 6.Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China
推荐引用方式 GB/T 7714	Qi, Feng,Li, Jia,Qi, Zhuoran,et al. Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma[J]. Research,2023,6.
APA	Qi, Feng., Li, Jia., Qi, Zhuoran., Zhang, Jian., Zhou, Bin., ... & Xia, Jinglin. (2023). Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma. Research, 6.
MLA	Qi, Feng,et al."Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma".Research 6(2023).