Integrated metabolomics and proteomics highlight altered nicotinamide and polyamine pathways in lung adenocarcinoma

Johannes F. Fahrmann, Dmitry Grapov, Kwanjeera Wanichthanarak, Brian C. DeFelice, Michelle R. Salemi, William N. Rom, David R. Gandara, Brett S. Phinney, Oliver Fiehn, Harvey Pass, Suzanne Miyamoto

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Lung cancer is the leading cause of cancer mortality in the United States with non-small cell lung cancer 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 s-adenosylmethionine/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 accompany early stage lung tumorigenesis and highlight potential therapeutic targets.

Original languageEnglish (US)
Pages (from-to)271-280
Number of pages10
JournalCarcinogenesis
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2017

ASJC Scopus subject areas

  • Cancer Research

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    Fahrmann, J. F., Grapov, D., Wanichthanarak, K., DeFelice, B. C., Salemi, M. R., Rom, W. N., Gandara, D. R., Phinney, B. S., Fiehn, O., Pass, H., & Miyamoto, S. (2017). Integrated metabolomics and proteomics highlight altered nicotinamide and polyamine pathways in lung adenocarcinoma. Carcinogenesis, 38(3), 271-280. https://doi.org/10.1093/carcin/bgw205