Liquid chromatography/mass spectrometry methods for measuring dipeptide abundance in non-small-cell lung cancer.

Abstract

RATIONALE:

Metabolomic profiling is a promising methodology of identifying candidate biomarkers for disease detection and monitoring. Although lung cancer is among the leading causes of cancer-related mortality worldwide, the lung tumor metabolome has not been fully characterized.

METHODS:

We utilized a targeted metabolomic approach to analyze discrete groups of related metabolites. We adopted a dansyl [5-(dimethylamino)-1-naphthalene sulfonamide] derivatization with liquid chromatography/mass spectrometry (LC/MS) to analyze changes of metabolites from paired tumor and normal lung tissues. Identification of dansylated dipeptides was confirmed with synthetic standards. A systematic analysis of retention times was required to reliably identify isobaric dipeptides. We validated our findings in a separate sample cohort.

RESULTS:

We produced a database of the LC retention times and MS/MS spectra of 361 dansyl dipeptides. Interpretation of the spectra is presented. Using this standard data, we identified a total of 279 dipeptides in lung tumor tissue. The abundance of 90 dipeptides was selectively increased in lung tumor tissue compared to normal tissue. In a second set of validation tissues, 12 dipeptides were selectively increased.

CONCLUSIONS:

A systematic evaluation of certain metabolite classes in lung tumors may identify promising disease-specific metabolites. Our database of all possible dipeptides will facilitate ongoing translational applications of metabolomic profiling as it relates to lung cancer.

• Authors: Manhong Wu, Yue Xu, William L Fitch, Ming Zheng, Robert E Merritt, Joseph B Shrager, Weiruo Zhang, David L Dill, Gary Peltz, Chuong D Hoang
• Journal: Rapid communications in mass spectrometry : RCM (Rapid Commun Mass Spectrom) Vol. 27 Issue 18 Pg. 2091-2098 (Sep 30 2013) ISSN: 1097-0231 [Electronic] England
• PMID: 23943330 (Publication Type: Evaluation Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 John Wiley & Sons, Ltd.

Chemical References

• Biomarkers
• Dipeptides

Topics

• Biomarkers (chemistry, metabolism)
• Carcinoma, Non-Small-Cell Lung (chemistry, metabolism)
• Chromatography, High Pressure Liquid (methods)
• Cohort Studies
• Dipeptides (chemistry, metabolism)
• Humans
• Lung Neoplasms (chemistry, metabolism)
• Metabolomics (methods)
• Tandem Mass Spectrometry (methods)