In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 423-423
Abstract:
Development of biomarkers for the responses to radiation has relevance to assessment of patient course and outcome after radiation therapy, as well as to other radiologic events including accidental and terrorist. The purpose of this study was to extend the biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation (TBI) at Memorial Sloan Kettering prior to bone marrow transplantation at 4-6h post irradiation (a single dose of 125cGy) and 24h (three fractions of 125cGy each). Patient diagnoses include leukemias (ALL, AML, and CML), non-hodgkins lymphoma, myelodysplastic syndrome, aplastic anemia, and essential thrombocytopenia. Global metabolomic profiling was obtained through analysis with Ultra Performance Liquid Chromatography (UPLC) coupled to time-of-flight mass spectrometry (TOFMS) (Waters). Peak alignment and deconvolution of the chromatographic data were conducted with MarkerLynx software (Waters, MA). Prior to further analysis, each sample was normalized to its respective creatinine. Ions with non-zero abundance values in at least 75% of samples in both groups were analyzed for statistical significance via the nonparametric Kolmogorov-Smirnov test for equality of probability distributions on the log-transformed dataset. Statistical significance for ions with non-zero abundance values in at least 75% of samples in only one group were analyzed categorically for presence (i.e. non-zero abundance) via the Fisher's exact test. Biomarker candidates were verified by tandem mass spectrometry (MS/MS) by comparison to pure chemicals and quantification of the markers was conducted with the triple quadrupole mass spectrometer XEVO TQ MS (Waters). Validated and quantified biomarkers include L-Octanoylcarnitine, Hypoxanthine, Trimethyl-L-Lysine, Acetyl-carnitine, Decanoylcarnitine, Pantothenic acid, Hippuric acid, Uric acid, and Xanthine, and thus contribute to the development of a human metabolomic signature following exposure to radiation, and can now be integrated with features including underlying disease status, gender, age, and outcome. Citation Format: Evagelia C. Laiakis, Tytus D. Mak, Sebastien Anizan, Sally A. Amundson, Christopher A. Barker, Suzanne L. Wolden, David J. Brenner, Albert J. Fornace. Metabolomic analysis of urine from patients undergoing total body irradiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 423. doi:10.1158/1538-7445.AM2013-423
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2013-423
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2013
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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