Abstract
Several studies have demonstrated that the metabolite composition of plasma may indicate the presence of lung cancer. The metabolism of cancer is characterized by an enhanced glucose uptake and glycolysis which is exploited by 18F-FDG positron emission tomography (PET) in the work-up and management of cancer. This study aims to explore relationships between 1H-NMR spectroscopy derived plasma metabolite concentrations and the uptake of labeled glucose (18F-FDG) in lung cancer tissue. PET parameters of interest are standard maximal uptake values (SUVmax), total body metabolic active tumor volumes (MATVWTB) and total body total lesion glycolysis (TLGWTB) values. Patients with high values of these parameters have higher plasma concentrations of N-acetylated glycoproteins which suggest an upregulation of the hexosamines biosynthesis. High MATVWTB and TLGWTB values are associated with higher concentrations of glucose, glycerol, N-acetylated glycoproteins, threonine, aspartate and valine and lower levels of sphingomyelins and phosphatidylcholines appearing at the surface of lipoproteins. These higher concentrations of glucose and non-carbohydrate glucose precursors such as amino acids and glycerol suggests involvement of the gluconeogenesis pathway. The lower plasma concentration of those phospholipids points to a higher need for membrane synthesis. Our results indicate that the metabolic reprogramming in cancer is more complex than the initially described Warburg effect.
Highlights
Metabolic adaptation in cancer cells was one of the first studied aspects of cancer
The focus of this study was to investigate relationships between the plasma metabolite concentrations obtained by 1H-NMR spectroscopy and the glycolytic activity measured by positron emission tomography (PET)-CT
It could be demonstrated by NMR metabolomics that a larger metabolic active tumor volume and/or a higher glycolytic burden seems to be associated with a higher glucose plasma concentration, indicative for an increased gluconeogenesis in this group of lung cancer patients
Summary
Metabolic adaptation in cancer cells was one of the first studied aspects of cancer. Otto Warburg discovered that, even in the presence of abundant oxygen, glycolysis leading to lactate via fermentation of pyruvate was often enhanced in cancer cells[1]. Cancer cells take up large amounts of glutamine, which is critical for the generation of anti-oxidants to remove reactive oxygen species (ROS) and for the synthesis of nonessential amino acids, nucleotides and fatty acids[11,12,17,18,19,20]. Metabolomics is defined as the “quantitative measurement of the dynamic multiparametric response of a living system to pathophysiological stimuli or genetic modification”[21] Pathophysiological conditions such as cancer results in altered levels of metabolites or different metabolic profiles. The study of altered metabolism in cancer cells is a relative new domain in oncology, several research groups were able to establish distinct metabolic profiles between cancer patients and healthy subjects using high resolution magic angle proton nuclear magnetic resonance (1H-NMR) spectroscopy[24,25,26,27,28,29]. This study may result in a deeper insight in the disturbed metabolism and guide us to the development of novel biomarkers and therapeutic agents for effective treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
