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

作     者：Feng Qi Jia Li Zhuoran Qi Jian Zhang Bin Zhou Biwei Yang Wenxing Qin Wenguo Cui Jinglin Xia Feng Qi;Jia Li;Zhuoran Qi;Jian Zhang;Bin Zhou;Biwei Yang;Wenxing Qin;Wenguo Cui;Jinglin Xia

作者机构：Department of OncologyRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200000China National Medical Center and National Clinical Research Center for Interventional MedicineLiver Cancer InstituteZhongshan HospitalFudan University180 Fenglin RoadShanghai 200032China Department of Hepatic Surgery VIEastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200433China Phase I Clinical Trial CenterFudan University Shanghai Cancer CenterDepartment of OncologyShanghai Medical CollegeFudan UniversityNo.270Dong’an RoadShanghai 200032China Department of OrthopaedicsShanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200000China Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang ProvinceThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000China 

出 版 物：《Research》 (研究（英文）)

年 卷 期：2023年第6卷第3期

页      面：433-449页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：the Natural Science Foundation of China(No.81972233 to J.X.) the Natural Science Foundation of China(No.82202874 to F.Q.) the Natural Science Foundation of China(No.81871920 to B.Y.) 

主　　题：metabolism Carcinoma alterations 

摘      要：Understanding the details of metabolic reprogramming in hepatocellular carcinoma(HCC)is critical to improve stratification for *** multiomics analysis and cross-cohort validation were performed to investigate the metabolic dysregulation of 562 HCC patients from 4 *** 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 *** 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 ***,the sensitivity of different clusters to metabolic inhibitors varied depending on their metabolic ***,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 *** conclusion,our results suggest the metabolic heterogeneity of HCC and make it possible to treat HCC patients precisely and effectively on specific metabolic characteristics.