Correlations between the metabolic profile and 18F-FDG-Positron Emission Tomography-Computed Tomography parameters reveal the complexity of the metabolic reprogramming within lung cancer patients

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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.

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