Urinary acylcarnitines are altered in human kidney cancer

Sheila Ganti, Sandra L. Taylor, Kyoungmi Kim, Charles L. Hoppel, Lining Guo, Joy Yang, Christopher P Evans, Robert H Weiss

Research output: Contribution to journalArticle

72 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2791-2800
Number of pages10
JournalInternational Journal of Cancer
Volume130
Issue number12
DOIs
StatePublished - Jun 15 2012

Fingerprint

Kidney Neoplasms
Urine
Neoplasms
Metabolomics
acylcarnitine
Cellular Structures
Tumor Biomarkers
Heterografts
Chromatography
Mass Spectrometry
Carbon
Drug Therapy
Therapeutics

Keywords

  • acylcarnitine
  • biomarker
  • fatty acid oxidation
  • kidney cancer
  • mass spectrometry
  • metabolism
  • metabolomics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Urinary acylcarnitines are altered in human kidney cancer. / Ganti, Sheila; Taylor, Sandra L.; Kim, Kyoungmi; Hoppel, Charles L.; Guo, Lining; Yang, Joy; Evans, Christopher P; Weiss, Robert H.

In: International Journal of Cancer, Vol. 130, No. 12, 15.06.2012, p. 2791-2800.

Research output: Contribution to journalArticle

Ganti S, Taylor SL, Kim K, Hoppel CL, Guo L, Yang J et al. Urinary acylcarnitines are altered in human kidney cancer. International Journal of Cancer. 2012 Jun 15;130(12):2791-2800. https://doi.org/10.1002/ijc.26274
Ganti, Sheila ; Taylor, Sandra L. ; Kim, Kyoungmi ; Hoppel, Charles L. ; Guo, Lining ; Yang, Joy ; Evans, Christopher P ; Weiss, Robert H. / Urinary acylcarnitines are altered in human kidney cancer. In: International Journal of Cancer. 2012 ; Vol. 130, No. 12. pp. 2791-2800.
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