Metabolomic Profiling of Plasma and Urine of Benzo(a)pyrene-Induced Mouse Models of Lung Cancer

Background

Lung cancer (LC) is one of the most common malignancies with a high fatality rate. The current study recognizes the important metabolites and metabolic pathways in the plasma and urine of a BaP-induced mice model of LC.

Methods and Results

LC was generated by administering BaP (50-mg/kg body weight, twice a week for 1 month) orally. Plasma and urine samples were collected after 4 months of BaP treatment and derivatized with BSTFA and 1% TMCS. The metabolomics analysis was performed by using the gas chromatography mass spectrometry (GC–MS), and metabolites were recognized by annotating the peaks with the NIST mass spectra. There were 19 compounds in plasma and 48 compounds in urine, belonging to amino acids, fatty acids, sugars, and some organic categories, showing significant metabolic perturbations. The PCA and PLS-DA models also suggest a perfect discrimination between the metabolites in the plasma and urine of control and tumor-bearing mice. The VIP plot identifies nine compounds in plasma and in urine with maximum VIP scores. The maximum AUC value compounds in plasma (trimethyl phosphate, L-isoleucine, L-proline, 3,3′-oxydipropanol, L-glutamic acid, and 9-octadecenoic acid) and in urine (glycine, L-aspartic acid, L-5-oxoproline, butanedioic acid, glyceric acid, and butanoic acid) could be used as potential diagnostic markers in LC.

Conclusions

The metabolomics profiling of plasma and urine suggests a significant alteration in the relative abundance of fatty acids, sugars, and amino acids as well as potential biomarkers for the detection of LC.