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ResearchIn-Press PreviewMetabolismOncology Open Access | 10.1172/JCI165028
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Zheng, L. in: JCI | PubMed | Google Scholar |
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Zhu, Z. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Sneh, T. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Zhang, W. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Wang, Z. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Wu, G. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by He, W. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Qi, H. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Wang, H. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Wu, X. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Fernández-García, J. in: JCI | PubMed | Google Scholar |
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Abramovich, I. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Xu, Y. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Zhang, J. in: JCI | PubMed | Google Scholar
1Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Ruth and Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
3Shanghai Tong Ren Hospital and Clinical Research Institute, Shanghai Jiao Tong University, Shanghai, China
4Department of Pathology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
5Department of Urology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
6Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
7Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
8Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, United States of America
Find articles by Gottlieb, E. in: JCI | PubMed | Google Scholar |
Published April 13, 2023 - More info
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.