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Purpose <p>To evaluate hexosamine biosynthetic pathway (HBP) involvement in high-fluorodeoxyglucose (FDG)-uptake lung adenocarcinoma.</p> Methods <p>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.</p> Results <p>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 tissues 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 &lt; 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.</p> Conclusions <p>Hypermetabolic adenocarcinoma may be associated with intensified glycolysis and HBP activation.</p>

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Elevated glucose metabolism via the hexosamine biosynthesis pathway: A metabolic signature of high-fluorodeoxyglucose-uptake lung adenocarcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月10日

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  • Hikaru Watanabe,
  • Hideki Makinoshima,
  • Naoki Kanauchi,
  • Takanobu Kabasawa,
  • Jun Suzuki,
  • Satoshi Takamori,
  • Takayuki Sasage,
  • Kohei Abe,
  • Kazumasa Hoshijima,
  • Tetsuro Uchida,
  • Tomoyoshi Soga,
  • Satoshi Shiono

摘要

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 tissues 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.