Uracil as a biomarker for spatial pyrimidine metabolism in the development of gingivobuccal oral squamous cell carcinoma.
GB-OSCC
Nuclear magnetic resonance
P2Y6receptor
Tumor microenvironment
Uracil
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 May 2024
21 May 2024
Historique:
received:
26
12
2023
accepted:
16
05
2024
medline:
22
5
2024
pubmed:
22
5
2024
entrez:
21
5
2024
Statut:
epublish
Résumé
No biomarker has yet been identified that allows accurate diagnosis and prognosis of oral cancers. In this study, we investigated the presence of key metabolites in oral cancer using proton nuclear magnetic resonance (NMR) spectroscopy to identify metabolic biomarkers of gingivobuccal oral squamous cell carcinoma (GB-OSCC). NMR spectroscopy revealed that uracil was expressed in 83.09% of tumor tissues and pyrimidine metabolism was active in GB-OSCC; these results correlated well with immunohistochemistry (IHC) and RNA sequencing data. Based on further gene and protein analyses, we proposed a pathway for the production of uracil in GB-OSCC tissues. Uridinetriphosphate (UTP) is hydrolyzed to uridine diphosphate (UDP) by CD39 in the tumor microenvironment (TME). We hypothesized that UDP enters the cell with the help of the UDP-specific P2Y6 receptor for further processing by ENTPD4/5 to produce uracil. As the ATP reserves diminish, the weakened immune cells in the TME utilize pyrimidine metabolism as fuel for antitumor activity, and the same mechanism is hijacked by the tumor cells to promote their survival. Correspondingly, the differential expression of ENTPD4 and ENTPD5 in immune and tumor cells, respectively, indicatedtheir involvement in disease progression. Furthermore, higher uracil levels were detected in patients with lymph node metastasis, indicating that metastatic potential is increased in the presence of uracil. The presence of uracil and/or expression patterns of intermediate molecules in purine and pyrimidine pathways, such asCD39, CD73, and P2Y6 receptors together with ENTPD4 and ENTPD5, hold promise as biomarker(s) for oral cancer diagnosis and prognosis.
Identifiants
pubmed: 38773214
doi: 10.1038/s41598-024-62434-z
pii: 10.1038/s41598-024-62434-z
doi:
Substances chimiques
pyrimidine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11609Subventions
Organisme : Department of Biotechnology, Ministry of Science and Technology, India
ID : No./BT/Med-II/NIBMG/SyMeC/2014/Vol II).
Organisme : Department of Biotechnology, Ministry of Science and Technology, India
ID : No./BT/Med-II/NIBMG/SyMeC/2014/Vol II).
Informations de copyright
© 2024. The Author(s).
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