Circulating biomarkers of kidney tumors in TSC (tuberous sclerosis complex) patients
Rubtsova, V. I.; Chun, Y.; Kim, J.; Ramirez, C. B.; Jung, S.; Cassidy, E.; Rushing, G.; Aguiar, D. J.; Lau, W. L.; Ahdoot, R. S.; Smith, M.; Lee, S.-G.; Jang, C.; Lee, G.
Show abstract
Patients with tuberous sclerosis complex (TSC) develop an array of multi-organ disease manifestations, with angiomyolipomas (AML) and cysts in the kidneys being one of the most common and deadly. Early and regular AML/cyst detection and monitoring are vital in lowering TSC patient morbidity and mortality. However, current standard of care for imaging-based methods are not designed for rapid screening, posing challenges for early detection. To identify potential diagnostic screening biomarkers of AML/cysts, we performed global untargeted metabolomics in blood samples from 283 kidney AML/cyst-positive or -negative TSC patients using mass spectrometry. We identified seven highly sensitive chemical features, including octanoic acid, that predict kidney AML/cysts in TSC patients. Patients with elevated octanoic acid have lower levels of very long-chain fatty acids (VLCFAs), suggesting that dysregulated peroxisome activity leads to overproduction of octanoic acid via VLCFA oxidation. This study highlights serum metabolites as novel biomarkers for TSC kidney tumor diagnosis and offers valuable metabolic insights into the disease.
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