Dataset Information

Non-invasive urinary metabolomic profiling identifies diagnostic and prognostic markers in lung cancer

ABSTRACT: Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1500 Da) were measured in urine collected from 469 lung cancer patients and 536 population controls using unbiased liquid chromatography-mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further validated in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared to the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA), were each significantly (P <0.00001) elevated in non–small cell lung cancer (NSCLC) and associated with worse prognosis (hazard ratio (HR) =1.81 [P =0.0002], and 1.54 [P =0.025], respectively). Creatine riboside was the strongest classifier of lung cancer status in all and stage I–II cases, important for early detection, and also associated with worse prognosis in stage I–II lung cancer (HR =1.71, P =0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 – 0.99. Both metabolites were significantly (P <0.03) enriched in tumor tissue compared to adjacent non-tumor tissue (N =48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis.

INSTRUMENT(S): Xevo QTof MS (Waters)

PROVIDER: MTBLS28 | MetaboLights | 2014-05-06

REPOSITORIES: MetaboLights

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Source:

			Action	DRS
	20080809_NIH_EWY_POS_0008.mzML	Mzml
	20080809_NIH_EWY_POS_000801.CDF	Other
	20080809_NIH_EWY_POS_0009.mzML	Mzml
	20080809_NIH_EWY_POS_000901.CDF	Other
	20080809_NIH_EWY_POS_0010.mzML	Mzml

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Noninvasive urinary metabolomic profiling identifies diagnostic and prognostic markers in lung cancer.

Mathé Ewy A EA Patterson Andrew D AD Haznadar Majda M Manna Soumen K SK Krausz Kristopher W KW Bowman Elise D ED Shields Peter G PG Idle Jeffrey R JR Smith Philip B PB Anami Katsuhiro K Kazandjian Dickran G DG Hatzakis Emmanuel E Gonzalez Frank J FJ Harris Curtis C CC

Cancer research 20140415 12

Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1,500 Da) were measured in urine collected from 469 patients with lung cancer and 536 population controls using unbiased liquid chromatography/mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time p ...[more]

PMID: 24736543

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