Lung cancer is the leading cause of
cancer mortality in the United States with
non-small cell lung cancer (NSCLC)
adenocarcinoma being the most common histological type. Early perturbations in cellular metabolism are a hallmark of
cancer, but the extent of these changes in early stage
lung adenocarcinoma remains largely unknown. In the current study, an integrated metabolomics and proteomics approach was utilized to characterize the biochemical and molecular alterations between malignant and matched control tissue from 27 subjects diagnosed with early stage
lung adenocarcinoma. Differential analysis identified 71 metabolites and 1102
proteins that delineated
tumor from control tissue. Integrated results indicated four major metabolic changes in early stage
adenocarcinoma: (1) increased glycosylation and glutaminolysis; (2) elevated Nrf2 activation; (3) increase in nicotinic and
nicotinamide salvaging pathways; and (4) elevated
polyamine biosynthesis linked to differential regulation of the SAM/
nicotinamide methyl-donor pathway. Genomic data from publicly available databases were included to strengthen proteomic findings. Our findings provide insight into the biochemical and molecular biological reprogramming that may accompanies early stage lung
tumorigenesis and highlight potential therapeutic targets.