Urinary acylcarnitines are altered in human kidney cancer
Open Access
- 5 July 2011
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 130 (12), 2791-2800
- https://doi.org/10.1002/ijc.26274
Abstract
Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length‐dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF‐κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer.Keywords
This publication has 27 references indexed in Scilit:
- Urine Metabolomic Analysis Identifies Potential Biomarkers and Pathogenic Pathways in Kidney CancerOMICS: A Journal of Integrative Biology, 2011
- Plasma Acylcarnitine Profiles Suggest Incomplete Long-Chain Fatty Acid β-Oxidation and Altered Tricarboxylic Acid Cycle Activity in Type 2 Diabetic African-American WomenJournal of Nutrition, 2009
- Grade-dependent Proteomics Characterization of Kidney CancerMolecular & Cellular Proteomics, 2009
- A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin ResistanceCell Metabolism, 2009
- Urine Metabolomics Analysis for Kidney Cancer Detection and Biomarker DiscoveryMolecular & Cellular Proteomics, 2009
- The Mitochondrial Uncoupling Protein-2 Promotes Chemoresistance in Cancer CellsCancer Research, 2008
- Peroxisomal branched chain fatty acid ?-oxidation pathway is upregulated in prostate cancerThe Prostate, 2004
- HK-2: An immortalized proximal tubule epithelial cell line from normal adult human kidneyKidney International, 1994
- Alterations of serum and urinary carnitine profiles in cancer patients: hypothesis of possible significance.Journal of the American College of Nutrition, 1989
- On the Origin of Cancer CellsScience, 1956