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Integrated ionization approach for RRLC-MS/MS-based metabonomics: finding potential biomarkers for lung cancer.
- Source :
-
Journal of proteome research [J Proteome Res] 2010 Aug 06; Vol. 9 (8), pp. 4071-81. - Publication Year :
- 2010
-
Abstract
- An integrated ionization approach of electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), and atmospheric pressure photoionization (APPI) combining with rapid resolution liquid chromatography mass spectrometry (RRLC-MS) has been developed for performing global metabonomic analysis on complex biological samples. This approach was designed to overcome the low ionization efficiencies of endogenous metabolites due to diverse physicochemical properties as well as ion suppression, and obtain comprehensive metabolite profiles in LC-MS analysis. Ionization capability and applicability were manifested by improved ionization efficiency and enlarged metabolite coverage in analysis on typical urinary metabolite standards and urine samples from healthy volunteers. The method was validated by the limit of detection and precision. When applied to the global metabonomic studies of lung cancer, more comprehensive biomarker candidates were obtained to reflect metabolic traits between healthy volunteers and lung cancer patients, including 74 potential biomarkers in positive ion mode and 59 in negative ion mode. Taking identical potential biomarkers of any two or three ionization methods into account, analysis using ESI-MS in positive (+) and negative (-) ion mode contributed to 70 and 64% of the total potential biomarkers, respectively. The biomarker discovery capability of (+/-) APCI-MS accounted for 45 and 42% of the overall; meanwhile (+/-) APPI-MS amounted for 39 and 54%. These results indicated that potential biomarkers with vital biological information could be missed if only a single ionization method was used. Furthermore, 11 potential biomarkers were identified including amino acids, nucleosides, and a metabolite of indole. They revealed elevated amino acid and nucleoside metabolism as well as protein degradation in lung cancer patients. This proposed approach provided a more comprehensive picture of the metabolic changes and further verified identical biomarkers that were obtained simultaneously using different ionization methods.
- Subjects :
- Aged
Biomarkers, Tumor analysis
Case-Control Studies
China
Chromatography, Liquid methods
Humans
Middle Aged
Multivariate Analysis
Spectrometry, Mass, Electrospray Ionization methods
Tandem Mass Spectrometry methods
Biomarkers, Tumor urine
Lung Neoplasms diagnosis
Lung Neoplasms urine
Metabolomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3907
- Volume :
- 9
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of proteome research
- Publication Type :
- Academic Journal
- Accession number :
- 20560663
- Full Text :
- https://doi.org/10.1021/pr100265g