Radiation-induced changes in salivary metabolite profile and pathways in head and neck cancer patients
Ramsay, Saga; Hyvärinen, Eelis; González-Arriagada, Wilfredo; Salo, Tuula; Ajudarte Lopes, Marcio; Mikkonen, Jopi J W; Kashyap, Bina; Kullaa, Arja M (2025-02-21)
Springer
21.02.2025
Ramsay, S., Hyvärinen, E., González-Arriagada, W. et al. Radiation-induced changes in salivary metabolite profile and pathways in head and neck cancer patients. Clin Oral Invest 29, 145 (2025). https://doi.org/10.1007/s00784-025-06225-4
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https://creativecommons.org/licenses/by/4.0/
© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202502241803
https://urn.fi/URN:NBN:fi:oulu-202502241803
Tiivistelmä
Abstract
Introduction:
This longitudinal study assessed the salivary metabolic profile in patients with head and neck cancer (HNC) treated with radiotherapy (RT). This study aims to investigate salivary metabolites and biological oral pathways induced by RT.
Methods:
Clinical data and unstimulated whole-mouth saliva (USWMS) were obtained from 45 HNC patients before, during, and one week after the RT. Data was also collected from 30 healthy controls. NMR spectroscopy identified and quantified 24 metabolites. Spearman’s rank correlation analysis and pathway enrichment analysis (MetaboAnalyst 6.0) was performed to check the effect of cancer therapy on the correlation and pathways of different salivary metabolites.
Results:
Of 24 metabolites identified, 17 salivary metabolites showed a consistent decrease in the concentration during and after treatment of HNC patients. The metabolite proline decreased, whereas fucose and 1,2-Propanediol were increased in the saliva causing altered redox balance and abnormal fucosylation in HNC patients compared to controls. Spearman correlation analysis indicated changes between pyruvate and some other metabolites, including alanine, trimethylamine, choline, taurine, and succinate, during RT. Five pathways (Pyruvate metabolism; Glycolysis / Gluconeogenesis; Glycine, serine, and threonine metabolism; Glyoxylate and dicarboxylate metabolism; and Alanine, aspartate and glutamate metabolism) are affected, demonstrating the metabolic dysregulation due to RT. The pyruvate metabolism was overpresented with the high Pathway Impact score.
Conclusion:
Salivary metabolomics analysis revealed significant alterations in the metabolic profile of HNC patients undergoing RT, providing valuable insights into treatment-induced oral pathobiological changes. Alterations in salivary pathways during RT suggest disturbances in redox homeostasis, oxidative stress, and inflammation. The ability to monitor salivary metabolites and pathways non-invasively holds promise to personalized medicine in HNC treatment by enabling early detection of treatment-related toxicities, monitoring treatment response, and tailoring interventions to patient needs.
Introduction:
This longitudinal study assessed the salivary metabolic profile in patients with head and neck cancer (HNC) treated with radiotherapy (RT). This study aims to investigate salivary metabolites and biological oral pathways induced by RT.
Methods:
Clinical data and unstimulated whole-mouth saliva (USWMS) were obtained from 45 HNC patients before, during, and one week after the RT. Data was also collected from 30 healthy controls. NMR spectroscopy identified and quantified 24 metabolites. Spearman’s rank correlation analysis and pathway enrichment analysis (MetaboAnalyst 6.0) was performed to check the effect of cancer therapy on the correlation and pathways of different salivary metabolites.
Results:
Of 24 metabolites identified, 17 salivary metabolites showed a consistent decrease in the concentration during and after treatment of HNC patients. The metabolite proline decreased, whereas fucose and 1,2-Propanediol were increased in the saliva causing altered redox balance and abnormal fucosylation in HNC patients compared to controls. Spearman correlation analysis indicated changes between pyruvate and some other metabolites, including alanine, trimethylamine, choline, taurine, and succinate, during RT. Five pathways (Pyruvate metabolism; Glycolysis / Gluconeogenesis; Glycine, serine, and threonine metabolism; Glyoxylate and dicarboxylate metabolism; and Alanine, aspartate and glutamate metabolism) are affected, demonstrating the metabolic dysregulation due to RT. The pyruvate metabolism was overpresented with the high Pathway Impact score.
Conclusion:
Salivary metabolomics analysis revealed significant alterations in the metabolic profile of HNC patients undergoing RT, providing valuable insights into treatment-induced oral pathobiological changes. Alterations in salivary pathways during RT suggest disturbances in redox homeostasis, oxidative stress, and inflammation. The ability to monitor salivary metabolites and pathways non-invasively holds promise to personalized medicine in HNC treatment by enabling early detection of treatment-related toxicities, monitoring treatment response, and tailoring interventions to patient needs.
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