Circulating biomarkers of kidney angiomyolipoma and cysts in tuberous sclerosis complex patients
Varvara I. Rubtsova,
Yujin Chun,
Joohwan Kim,
Cuauhtemoc B. Ramirez,
Sunhee Jung,
Wonsuk Choi,
Miranda E. Kelly,
Miranda L. Lopez,
Elizabeth Cassidy,
Gabrielle Rushing,
Dean J. Aguiar,
Wei Ling Lau,
Rebecca S. Ahdoot,
Moyra Smith,
Aimee L. Edinger,
Sang-Guk Lee,
Cholsoon Jang,
Gina Lee
Affiliations
Varvara I. Rubtsova
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA; Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA, USA
Yujin Chun
Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA, USA
Joohwan Kim
Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA, USA
Cuauhtemoc B. Ramirez
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA; Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA, USA
Sunhee Jung
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA
Wonsuk Choi
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA
Miranda E. Kelly
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA
Miranda L. Lopez
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA
Elizabeth Cassidy
TSC Alliance, Silver Spring, MD, USA
Gabrielle Rushing
TSC Alliance, Silver Spring, MD, USA
Dean J. Aguiar
TSC Alliance, Silver Spring, MD, USA
Wei Ling Lau
Division of Nephrology, Department of Medicine, School of Medicine, University of California Irvine, Irvine, CA, USA
Rebecca S. Ahdoot
Division of Nephrology, Department of Medicine, School of Medicine, University of California Irvine, Irvine, CA, USA
Moyra Smith
Division of Genetics and Metabolism, Department of Pediatrics, School of Medicine, University of California Irvine, Irvine, CA, USA
Aimee L. Edinger
Department of Developmental and Cell Biology, School of Biological Sciences, University of California Irvine, Irvine, CA, USA; Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA
Sang-Guk Lee
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA; Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea; Corresponding author
Cholsoon Jang
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA; Center for Complex Biological Systems, University of California Irvine, Irvine, CA, USA; Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, USA; Corresponding author
Gina Lee
Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA, USA; Chao Family Comprehensive Cancer Center, University of California Irvine, Irvine, CA, USA; Center for Complex Biological Systems, University of California Irvine, Irvine, CA, USA; Center for Epigenetics and Metabolism, University of California Irvine, Irvine, CA, USA; Corresponding author
Summary: Patients with tuberous sclerosis complex (TSC) develop multi-organ disease manifestations, with kidney angiomyolipomas (AML) and cysts being one of the most common and deadly. Early and regular AML/cyst detection and monitoring are vital to lower TSC patient morbidity and mortality. However, the current standard of care involves imaging-based methods that 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 7 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. These data highlight AML/cysts blood biomarkers for TSC patients and offers valuable metabolic insights into the disease.
