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Elevated glucose metabolism via the hexosamine biosynthesis pathway: A metabolic signature of high-fluorodeoxyglucose-uptake lung adenocarcinoma
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DOI：10.1007/s00595-026-03276-2.png)
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Abstract
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Purpose To evaluate hexosamine biosynthetic pathway (HBP) involvement in high-fluorodeoxyglucose (FDG)-uptake lung adenocarcinoma. Methods We conducted metabolomic analysis to evaluate the HBP in patients with lung adenocarcinoma, who underwent preoperative 18-FDG positron emission tomography. Capillary electrophoresis-time-of-flight mass spectrometry was done to obtain 511 small-molecule metabolite spectra, and a principal component analysis was performed. Results We examined 80 tissue samples: 40 tumor-adjacent non-tumor tissue samples and 40 resected lung adenocarcinomas. The principal component analysis confirmed good clustering between the tumor and non-tumor tissues. The non-tumor tis-sues comprised uniform materials, whereas the tumor tissues comprised a mixture of materials. Heatmaps for 50 metabolites revealed lower glucose and citrate levels and higher levels of lactate, glycolysis metabolites, succinate, fumarate, adenosine di- and -monophosphate, and all essential amino acids in the tumor tissues than the non-tumor tissues. HBP intermediate and uridine diphosphate N-acetylglucosamine levels were also higher in the tumor tissues. Both lactate and HBP intermediate levels were higher in hypermetabolic tumor tissues (standardized uptake value >= 3) than in non-hypermetabolic tumor tissues (standardized uptake value < 3). Low-FDG-uptake cells showed strong expression for glucose transporter SLC2A1 and weak expression for O-linked N-acetylglucosamine, whereas high-FDG-uptake cells showed strong expression for both markers. Conclusions Hypermetabolic adenocarcinoma may be associated with intensified glycolysis and HBP activation
Keywords:
Metabolome analysis
Hexosamine biosynthesis pathway
Warburg effect
Lung adenocarcinoma
18-fluoro-2-deoxyglucose positron emission tomography
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