title: Integrated Metabolomics and Proteomics Highlight Altered Nicotinamide- and Polyamine Pathways in Lung Adenocarcinoma.
abstract: 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.
authors.affiliation: University of California, Davis, West Coast Metabolomics Center, Davis, California.
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Fahrmann
authors.affiliation: CDS Creative Data Solutions, Ballwin, MO.
authors.forename: Dmitry D
authors.initials: DD
authors.lastname: Grapov
authors.affiliation: University of California, Davis, West Coast Metabolomics Center, Davis, California.
authors.forename: Kwanjeera
authors.initials: K
authors.lastname: Wanichthanarak
authors.affiliation: University of California, Davis, West Coast Metabolomics Center, Davis, California.
authors.forename: Brian C
authors.initials: BC
authors.lastname: DeFelice
authors.affiliation: Genome Center Proteomics Core Facility.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Salemi
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep, NYU School of Medicine, New York, NY, USA.
authors.forename: William N
authors.initials: WN
authors.lastname: Rom
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California, Davis Medical Center, Sacramento, California.
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
authors.affiliation: Genome Center Proteomics Core Facility.
authors.forename: Brett S
authors.initials: BS
authors.lastname: Phinney
authors.affiliation: University of California, Davis, West Coast Metabolomics Center, Davis, California.|Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi-Arabia.
authors.forename: Oliver
authors.initials: O
authors.lastname: Fiehn
authors.affiliation: Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Langone Medical Center, New York University, New York, NY, USA.
authors.forename: Harvey
authors.initials: H
authors.lastname: Pass
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California, Davis Medical Center, Sacramento, California smiyamoto@ucdavis.edu.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Miyamoto
keywords: Lung Adenocarcinoma; Metabolomics; Proteomics