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Reporting on FH-deficient renal cell carcinoma using circulating succinylated metabolites
Divya Bezwada1, James Brugarolas2,3
1Children's Medical Center Research Institute.
Abstract:
Fumarate hydratase-deficient (FH-deficient) renal cell carcinoma (RCC) represents a particularly aggressive form of kidney cancer. FH-deficient RCC arises in the setting of germline, or solely somatic, mutations in the FH gene, a two-hit tumor suppressor gene. Early detection can be curative, but there are no biomarkers, and in the sporadic setting, establishing a diagnosis of FH-deficient RCC is challenging. In this issue of the JCI, Zheng, Zhu, and co-authors report untargeted plasma metabolomic analyses to identify putative biomarkers. They discovered two plasma metabolites directly linked to fumarate overproduction by tumor cells, succinyl-adenosine and succinic-cysteine, which correlate with tumor burden. The identification of circulating biomarkers of FH-deficient RCC may aid in the diagnosis of FH-deficient RCC and provide a means for longitudinal follow-up.
Insights
New biomarkers for aggressive fumarate hydratase-deficient (FH)-deficient renal cell carcinoma (RCC) have been identified. These plasma metabolites, succinyl-adenosine and succinic-cysteine, may aid in early diagnosis and monitoring of this challenging kidney cancer.
Area of Science:
- Oncology
- Metabolomics
- Genetics
Background:
- Fumarate hydratase-deficient (FH)-deficient renal cell carcinoma (RCC) is an aggressive kidney cancer linked to FH gene mutations.
- Current diagnostic challenges exist, especially in sporadic cases, due to the lack of reliable biomarkers.
- Early detection is crucial for curative treatment outcomes in FH-deficient RCC.
Purpose of the Study:
- To identify novel plasma biomarkers for the early detection and monitoring of FH-deficient RCC.
- To investigate the correlation between specific metabolites and tumor burden in FH-deficient RCC patients.
Main Methods:
- Untargeted plasma metabolomic analyses were performed.
- Identification of metabolites directly associated with fumarate overproduction by tumor cells.
- Correlation analysis between identified metabolites and tumor burden.
Main Results:
- Two novel plasma metabolites, succinyl-adenosine and succinic-cysteine, were discovered.
- These metabolites are directly linked to fumarate overproduction characteristic of FH-deficient RCC.
- The levels of these biomarkers correlate with tumor burden in patients.
Conclusions:
- Succinyl-adenosine and succinic-cysteine show promise as circulating biomarkers for FH-deficient RCC.
- These findings may facilitate earlier diagnosis and enable longitudinal follow-up of patients.
- The identified biomarkers could improve management strategies for this aggressive cancer.
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