Urine metabolomics analysis for kidney cancer detection and biomarker discovery

Kyoungmi Kim, Pavel Aronov, Stanislav O. Zakharkin, Danielle Anderson, Bertrand Perroud, Ian M. Thompson, Robert H Weiss

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

Renal cell carcinoma (RCC) accounts for 11,000 deaths per year in the United States. When detected early, generally serendipitously by imaging conducted for other reasons, long term survival is generally excellent. When detected with symptoms, prognosis is poor. Under these circumstances, a screening biomarker has the potential for substantial public health benefit. The purpose of this study was to evaluate the utility of urine metabolomics analysis for metabolomic profiling, identification of biomarkers, and ultimately for devising a urine screening test for RCC. Fifty urine samples were obtained from RCC and control patients from two institutions, and in a separate study, urine samples were taken from 13 normal individuals. Hydrophilic interaction chromatography-mass spectrometry was performed to identify small molecule metabolites present in each sample. Cluster analysis, principal components analysis, linear discriminant analysis, differential analysis, and variance component analysis were used to analyze the data. Previous work is extended to confirm the effectiveness of urine metabolomics analysis using a larger and more diverse patient cohort. It is now shown that the utility of this technique is dependent on the site of urine collection and that there exist substantial sources of variation of the urinary metabolomic profile, although group variation is sufficient to yield viable biomarkers. Surprisingly there is a small degree of variation in the urinary metabolomic profile in normal patients due to time since the last meal, and there is little difference in the urinary metabolomic profile in a cohort of pre- and postnephrectomy (partial or radical) renal cell carcinoma patients, suggesting that metabolic changes associated with RCC persist after removal of the primary tumor. After further investigations relating to the discovery and identity of individual biomarkers and attenuation of residual sources of variation, our work shows that urine metabolomics analysis has potential to lead to a diagnostic assay for RCC.

Original languageEnglish (US)
Pages (from-to)558-570
Number of pages13
JournalMolecular and Cellular Proteomics
Volume8
Issue number3
DOIs
StatePublished - Mar 2009

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Metabolomics
Kidney Neoplasms
Tumor Biomarkers
Renal Cell Carcinoma
Urine
Biomarkers
Analysis of Variance
Screening
Cells
Urine Specimen Collection
Cluster analysis
Discriminant Analysis
Discriminant analysis
Insurance Benefits
Public health
Metabolites
Chromatography
Principal Component Analysis
Hydrophobic and Hydrophilic Interactions
Principal component analysis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Analytical Chemistry

Cite this

Urine metabolomics analysis for kidney cancer detection and biomarker discovery. / Kim, Kyoungmi; Aronov, Pavel; Zakharkin, Stanislav O.; Anderson, Danielle; Perroud, Bertrand; Thompson, Ian M.; Weiss, Robert H.

In: Molecular and Cellular Proteomics, Vol. 8, No. 3, 03.2009, p. 558-570.

Research output: Contribution to journalArticle

Kim, Kyoungmi ; Aronov, Pavel ; Zakharkin, Stanislav O. ; Anderson, Danielle ; Perroud, Bertrand ; Thompson, Ian M. ; Weiss, Robert H. / Urine metabolomics analysis for kidney cancer detection and biomarker discovery. In: Molecular and Cellular Proteomics. 2009 ; Vol. 8, No. 3. pp. 558-570.
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