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Comparative metabolic analysis in head and neck cancer and the normal gingiva

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Abstract

Objectives

Chronic accumulation of lactate in malignant tumor tissue is associated with increased malignancy and radioresistance. For this study, biopsies of primary head and neck squamous cell carcinoma (HNSCC) and of the normal gingiva of the same patient were compared via metabolic profiling to the healthy gingiva from cancer-free patients.

Materials and methods

Cryobiopsies of 140 HNSCC patients were used to determine ATP, lactate, and glucose concentrations of the tumor and normal gingiva via induced metabolic bioluminescence imaging (imBI). Additionally, these metabolites were quantified in a collective of 79 healthy (non-tumor-bearing) patients. Furthermore, tumor samples were analyzed via immunofluorescence imaging and quantitative real-time PCR for the expression of lactate and glucose transporters.

Results

There were significant differences in ATP concentrations detectable between the tumor, normal gingiva of tumor patients, and gingiva from healthy patients. Lactate concentrations were significantly increased in tumor tissue compared to the normal gingiva of tumor patients as well as the gingiva from healthy patients. Concerning glucose, there was a significant decrease in glucose concentrations detectable in the tumor biopsies compared to the normal gingiva of tumor patients. On the other hand, tumor samples from patients revealed significantly elevated relative expression levels of monocarboxylate transporters (MCT-1 and MCT-4), as well as glucose transporters (GLUT-1 and GLUT-3) compared to the corresponding normal gingiva of each patient.

Conclusions

We could demonstrate that the lactate concentration in HNSCC correlates with primary tumor (T) stage.

Clinical relevance

The aim of this study was to identify metabolic parameters to improve early cancer diagnosis, allow predictions on the degree of malignancy, and contribute to a personalized tumor therapy.

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Acknowledgements

We wish to thank Anette Denner-Seckert for technical support.

Author information

Authors and Affiliations

  1. Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128, Mainz, Germany

    Nadine Fabienne Voelxen, Pascal Knopf, Maurice Henkel, Christina Appelhans, Stefan Walenta & Wolfgang Mueller-Klieser

  2. Department of Oral and Maxillofacial Surgery, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany

    Sebastian Blatt, Leonardo A. R. Righesso, Andreas Pabst & Jutta Goldschmitt

  3. Clinic for Oral and Maxillofacial Surgery, University of Marburg, Marburg, Germany

    Andreas Neff & Thomas Ziebart

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  1. Nadine Fabienne Voelxen
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  2. Sebastian Blatt
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  4. Maurice Henkel
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  9. Stefan Walenta
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  11. Wolfgang Mueller-Klieser
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Contributions

N.V., P.K., M.H., C.A., and J.G. performed the experiments and analyzed the data. N.V., W.M.-K., and S.W. wrote the paper. S.B. and T.Z. provided clinical information about patients and treatments. S.W. helped in the discussion. W.M.-K. and T.Z. designed the study, analyzed the data, and guided the research presented.

Corresponding author

Correspondence to Nadine Fabienne Voelxen.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Funding

This study was funded by Deutsche Forschungsgemeinschaft (DFG) German Research Foundation MU576/19-1.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The local ethics committee (Landesärztekammer Rheinland-Pfalz) approved the following experiments (Ethikvotum 837.837.11 (7924)). This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Voelxen, N.F., Blatt, S., Knopf, P. et al. Comparative metabolic analysis in head and neck cancer and the normal gingiva. Clin Oral Invest 22, 1033–1043 (2018). https://doi.org/10.1007/s00784-017-2185-0

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  • DOI: https://doi.org/10.1007/s00784-017-2185-0

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