ArticleThe Journal of clinical investigation2023
Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- Tislelizumab plus lenvatinib in advanced fumarate hydratase-deficient renal cell carcinoma: a single-arm, phase 2 trial with metabolic biomarker analysis.Nature communications · 2026Trial
- Fumarate-induced succination of A-kinase anchor protein 12 exacerbates renal inflammation and fibrosis.The Journal of clinical investigation · 2026Article
- Imaging findings in fumarate hydratase-deficient renal cell carcinoma: a case series of 11 patients.Abdominal radiology (New York) · 2026Article
- KAT2A Promotes the Progression of Renal Cell Carcinoma by Regulating the Succinylation of SERPINE2.The Kaohsiung journal of medical sciences · 2026Article
- Excess cysteine drives conjugate formation and impairs proliferation of NRF2-activated cancer cells.Nature metabolism · 2026Article
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Biochemical characterization of the FH variant p.Lys414Glu reveals loss of enzymatic function and disrupted multimerization.Molecular genetics and metabolism reports · 2026Article
- Succinate-driven virulence enhancement in hypervirulentMicrobiology spectrum · 2026Article
- Hereditary leiomyomatosis and renal cell carcinoma: a case report and literature review.Frontiers in urology · 2026Article
- Targeting CPS1 attenuates lung cancer metastasis by regulating EMT through an epigenetic mechanism.Theranostics · 2026Article
- Effects of Tumor-associatedArchives of Razi Institute · 2025Article
- Molecular and therapeutic landscape of non-clear cell renal carcinoma.Nature reviews. Urology · 2025Review
- False positive PET scan of hereditary leiomyomatosis and renal cell cancer: A case report.Radiology case reports · 2025Article
- Circulating proteins and metabolites panel for noninvasive preoperative diagnosis of epithelial ovarian cancer.BMC medicine · 2025Article
- Regulators of Cancer Progression: Succinylation.Cancers · 2025Review
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
- Proteomics and succinylation modification characterization in clear cell renal cell carcinoma.Discover oncology · 2025Article
- Comprehensive molecular profiling of FH-deficient renal cell carcinoma identifies molecular subtypes and potential therapeutic targets.Nature communications · 2025Article
- Circulating biomarkers for diagnosis and response to therapies in cancer patients.International review of cell and molecular biology · 2025Review
- Emerging roles of metabolic biomarkers in renal cell carcinoma: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 2 tumor-derived metabolites, succinyl-adenosine and succinic-cysteine, as excellent plasma biomarkers for early diagnosis. These 2 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.
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