Untargeted Metabolomics Profiling Identifies Putative Biomarkers for Early Detection of Lung Cancer

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NCI	CANCER-12

* FARE Award Winner

Authors

• M. Haznadar
• E. Mathe
• A.D. Patterson
• S. Manna
• E.D. Bowman
• K.W. Krausz
• J.R. Idle
• F.J. Gonzalez
• C.C. Harris

Abstract

Lung cancer remains the most common cause of cancer deaths world-wide. The specificity and robustness of early detection remains to be achieved. What we readily know is that cancer cells have a distinguishable metabolic fingerprint compared to normal cells. We conducted a first of its kind effort using mass spectrometry-based untargeted metabolomic profiling of 469 lung cancer patient and 536 healthy population control urines. We identified four putative biomarkers, high levels of which are associated with lung cancer diagnosis and poorer survival, Bonferroni corrected and independent of stage, smoking status, race and gender. Combination of the four metabolites resulted in better predictions, indicating that they are independent putative biomarkers. We then profiled the metabolome of 73, stage I lung tumors compared to adjacent normal tissue. Levels of two metabolites, Met A and C, were more highly prevalent in tumor compared to adjacent normal tissues (FC= 2.1 and 9.03, respectively, p-val <0.00001). These findings indicate that Mets A and C might be direct bi-products of tumor metabolism and are detectable in stage I tumors. Mets A and C, along with the other putative biomarkers identified in this study, may serve as diagnostic and prognostic indicators in early detection of lung cancer.

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