Detection of bladder cancer in human urine by metabolomic profiling using high performance liquid chromatography/mass spectrometry.
OBJECTIVE
The current use of cystoscopy for screening and detecting bladder cancer is invasive and expansive. Various urine based biomarkers have been used for this purpose with limited success. Metabolomics, ie metabonomics, is the quantitative measurement of the metabolic response to pathophysiological stimuli. This analysis provides a metabolite pattern that can be characteristic of various benign and malignant conditions. We evaluated high performance liquid chromatography coupled online with a mass spectrometer metabolomic approach to differentiate urine samples from healthy individuals and patients with bladder cancer.


METHODS
Urine specimens were collected from 48 healthy individuals and 41 patients with transitional cell carcinoma, and stored at -80C. Samples were analyzed using an Agilent 1100 Series high performance liquid chromatography system (Agilent Technologies, Santa Clara, California) coupled online with a hybrid triple-quad time-of-flight QSTAR XL mass spectrometer. At the time of analysis samples were thawed and centrifuged. The resulting total ion chromatograms of each sample were submitted for statistical analysis. For data interpretation in this study 2 statistical methods were used, that is principal component analysis and orthogonal partial least square-discriminate analysis.


RESULTS
Using positive ionization mass spectrometry orthogonal partial least square-discriminate analysis correctly predicted 48 of 48 healthy and 41 of 41 bladder cancer urine samples, while principal component analysis, which is an unsupervised profiling statistical method, confirmed these results and correctly predicted 46 of 48 healthy and 40 of 41 bladder cancer urine samples.


CONCLUSIONS
The results of this proof of concept study in a relatively small number of subjects indicate that metabolomics using high performance liquid chromatography-mass spectrometry has the potential to become a noninvasive early detection test for bladder cancer.
Issaq
Haleem J
HJ
Laboratory of Proteomics and Analytical Technologies, SAIC Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702, USA. issaqh@mail.ncifcrf.gov
Nativ
Ofer
O
Waybright
Timothy
T
Luke
Brian
B
Veenstra
Timothy D
TD
Issaq
Elias J
EJ
Kravstov
Alexander
A
Mullerad
Michael
M
D000368:Aged; D000369:Aged, 80 and over; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000652:urine*