机构：[1]Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China[2]Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China[3]Fujian Branch of Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Fujian Children’s Hospital, Fuzhou, Fujian, 350014, China[4]Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China[5]Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel[6]Hongqiao International Institute of Medicine, Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China7Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiaotong University,Shanghai, China[8]Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China[9]Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China浙江大学医学院附属第一医院[10]Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China[11]Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
Germline or somatic loss-of-function mutations of fumarate hydratase (FH) predispose patients to an aggressive form of renal cell carcinoma (RCC). Since other than tumor resection, there is no effective therapy for metastatic FH-deficient RCC, an accurate method for early diagnosis is needed. Although MRI or CT scans are offered, they cannot differentiate FH-deficient tumors from other RCCs. Therefore, finding noninvasive plasma biomarkers suitable for rapid diagnosis, screening and surveillance would improve clinical outcomes. Taking advantage of the robust metabolic rewiring that occurs in FH-deficient cells, we performed plasma metabolomics analysis and identified two tumor-derived metabolites, succinyl-adenosine and succinic-cysteine, as outstanding plasma biomarkers for early diagnosis (receiver operating characteristic area under curve (ROCAUC) = 0.98). These two molecules reliably reflected the FH mutation status and tumor mass. We further identified the enzymatic cooperativity by which these biomarkers are produced within the tumor microenvironment. Longitudinal monitoring of patients demonstrated that these circulating biomarkers can be used for reporting on treatment efficacy and identifying recurrent or metastatic tumors.
基金：
General Program from NSFC (No. 82073415 and No. 82173826), Israel Science Foundation
(ISF 2366/18), Youth Project (No. 81703089), International Cooperation and Exchanges of the
National Natural Science Foundation of China (NSFC No. 81861148026), Shanghai Oriental
Scholars Professorship, Key grant Project by State Commission of Science and Technology of
China (No. 2018ZX10302206-002-003) and National Major Science and Technology
Infrastructure of translational medicine (Shanghai) Open Project (TMSK-2021-208).
第一作者机构：[1]Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China[2]Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China[3]Fujian Branch of Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Fujian Children’s Hospital, Fuzhou, Fujian, 350014, China[4]Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China[*3]Department of Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, 1678 Dong Fang Road, Shanghai, 200127, China.
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China[2]Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China[3]Fujian Branch of Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine, Fujian Children’s Hospital, Fuzhou, Fujian, 350014, China[4]Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China[5]Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel[11]Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA[*1]Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA[*2]Department of Urology, Renji Hospital, 160 Pu Jian Road, Shanghai, 200127, China.[*3]Department of Pediatric Translational Medicine Institute, Shanghai Children’s Medical Center, 1678 Dong Fang Road, Shanghai, 200127, China.
推荐引用方式(GB/T 7714)：
Liang Zheng,Zi-Ran Zhu,Tal Sneh,et al.Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma[J].JOURNAL OF CLINICAL INVESTIGATION.2023,133(11):doi:10.1172/JCI165028.
APA：
Liang Zheng,Zi-Ran Zhu,Tal Sneh,Wei-Tuo Zhang,Zao-Yu Wang...&Eyal Gottlieb.(2023).Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma.JOURNAL OF CLINICAL INVESTIGATION,133,(11)
MLA：
Liang Zheng,et al."Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma".JOURNAL OF CLINICAL INVESTIGATION 133..11(2023)
医学