Circulating biomarkers of kidney angiomyolipoma and cysts in tuberous sclerosis complex patients.

Clinical genetics Endocrinology Pathophysiology

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
19 Jul 2024
Historique:
received: 26 02 2024
revised: 04 05 2024
accepted: 11 06 2024
medline: 19 7 2024
pubmed: 19 7 2024
entrez: 19 7 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1016/j.isci.2024.110265 PMID: 39027368 PMC: PMC11255849
pubmed: 39027368
doi: 10.1016/j.isci.2024.110265
pii: S2589-0042(24)01490-1
pmc: PMC11255849
doi:

Types de publication

Journal Article

Langues

eng

Pagination

110265

Informations de copyright

© 2024 The Authors.

Déclaration de conflit d'intérêts

The authors declare no competing interests.

Auteurs

Varvara I Rubtsova (VI)

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 (Y)

Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA, USA.

Joohwan Kim (J)

Department of Microbiology and Molecular Genetics, School of Medicine, University of California Irvine, Irvine, CA, USA.

Cuauhtemoc B Ramirez (CB)

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 (S)

Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA.

Wonsuk Choi (W)

Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA.

Miranda E Kelly (ME)

Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA.

Miranda L Lopez (ML)

Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, CA, USA.

Elizabeth Cassidy (E)

TSC Alliance, Silver Spring, MD, USA.

Gabrielle Rushing (G)

TSC Alliance, Silver Spring, MD, USA.

Dean J Aguiar (DJ)

TSC Alliance, Silver Spring, MD, USA.

Wei Ling Lau (WL)

Division of Nephrology, Department of Medicine, School of Medicine, University of California Irvine, Irvine, CA, USA.

Rebecca S Ahdoot (RS)

Division of Nephrology, Department of Medicine, School of Medicine, University of California Irvine, Irvine, CA, USA.

Moyra Smith (M)

Division of Genetics and Metabolism, Department of Pediatrics, School of Medicine, University of California Irvine, Irvine, CA, USA.

Aimee L Edinger (AL)

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 (SG)

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.

Cholsoon Jang (C)

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.

Gina Lee (G)

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.

Classifications MeSH