Mass spectrometry based proteome profiling of the exhaled breath condensate for lung cancer biomarkers search

Objectives Lung cancer is one of the most lethal cancers. Currently, there are no biomarkers for early detection, monitoring treatment response, and detecting recurrent lung cancer. We undertook this study to determine if 1H magnetic resonance spectroscopy (MRS) of sputum and exhaled breath condensate (EBC), as a noninvasive tool, can identify metabolic biomarkers of lung cancer. Materials and Methods Sputum and EBC samples were collected from 20 patients, comprising patients with pathologically confirmed non-small cell lung cancer ( n = 10) and patients with benign respiratory conditions ( n = 10). Both sputum and EBC samples were collected from 18 patients; 2 patients provided EBC samples only. 1H MR spectra were obtained on a Bruker Avance 400 MHz nuclear magnetic resonance (NMR) spectrometer. Sputum samples were further confirmed cytologically to distinguish between true sputum and saliva. Results In the EBC samples, median concentrations of propionate, ethanol, acetate, and acetone were higher in lung cancer patients compared to the patients with benign conditions. Median concentration of methanol was lower in lung cancer patients (0.028 mM) than in patients with benign conditions (0.067 mM; P = 0.028). In the combined sputum and saliva and the cytologically confirmed sputum samples, median concentrations of N-acetyl sugars, glycoprotein, propionate, lysine, acetate, and formate were lower in the lung cancer patients than in patients with benign conditions. Glucose was found to be consistently absent in the combined sputum and saliva samples (88%) as well as in the cytologically confirmed sputum samples (86%) of lung cancer patients. Conclusion Absence of glucose in sputum and lower concentrations of methanol in EBC of lung cancer patients discerned by 1H MRS may serve as metabolic biomarkers of lung cancer for early detection, monitoring treatment response, and detecting recurrence.

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Sub-nanoliter metabolomics via mass spectrometry to characterize volume-limited samples

Nature Communications ◽

10.1038/s41467-020-19444-y ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Yafeng Li ◽

Marcos Bouza ◽

Changsheng Wu ◽

Hengyu Guo ◽

Danning Huang ◽

...

Keyword(s):

Mass Spectrometry ◽

Stromal Cells ◽

Exhaled Breath Condensate ◽

Sample Volume ◽

Triboelectric Nanogenerator ◽

Exhaled Breath ◽

Nanoelectrospray Ionization ◽

External Stimuli ◽

Breath Condensate

Abstract The human metabolome provides a window into the mechanisms and biomarkers of various diseases. However, because of limited availability, many sample types are still difficult to study by metabolomic analyses. Here, we present a mass spectrometry (MS)-based metabolomics strategy that only consumes sub-nanoliter sample volumes. The approach consists of combining a customized metabolomics workflow with a pulsed MS ion generation method, known as triboelectric nanogenerator inductive nanoelectrospray ionization (TENGi nanoESI) MS. Samples tested with this approach include exhaled breath condensate collected from cystic fibrosis patients as well as in vitro-cultured human mesenchymal stromal cells. Both test samples are only available in minimum amounts. Experiments show that picoliter-volume spray pulses suffice to generate high-quality spectral fingerprints, which increase the information density produced per unit sample volume. This TENGi nanoESI strategy has the potential to fill in the gap in metabolomics where liquid chromatography-MS-based analyses cannot be applied. Our method opens up avenues for future investigations into understanding metabolic changes caused by diseases or external stimuli.

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