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Radiotherapy changes the salivary proteome in head and neck cancer patients: evaluation before, during, and after treatment

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Abstract

Objectives

Salivary glands are affected during radiotherapy in the head and neck region, leading to a reduction in salivary flow and changes its composition. Besides negatively affecting the oral soft tissues, this can also lead to dental impairment. Thus, we evaluated the effect of radiotherapy in the proteomic profile of the saliva in patients with head and neck cancer (HNC).

Materials and methods

HNC patients had their saliva collected before (BRT), during (2–5 weeks; DRT), and after (3–4 months; ART) radiotherapy. Saliva was also collected from healthy volunteers (control; C). Samples were processed for proteomic analysis.

Results

In total, 1055 proteins were identified, among which 46 were common to all groups, while 86, 86, 286, and 395 were exclusively found in C, BRT, DRT, and ART, respectively. Remarkably, alpha-enolase was increased 35-fold DRT compared with BRT, while proline-rich proteins were decreased. ART there was a 16-fold increase in scaffold attachment factor-B1 and a 3-fold decrease in alpha-enolase and several cystatins. When compared with C, salivary proteins of BRT patients showed increases cystatin-C, lysozyme C, histatin-1, and proline-rich proteins

Conclusion/clinical revelance

Both HNC and radiotherapy remarkably change the salivary protein composition. Altogether, our results, for the first time, suggest investigating alpha-enolase levels in saliva DRT in future studies as a possible biomarker and strategy to predict the efficiency of the treatment. Moreover, our data provide important insights for designing dental products that are more effective for these patients and contribute to a better understanding of the progressive changes in salivary proteins induced by radiotherapy.

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Acknowledgements

The authors are grateful especialy the trial participants and their families, and the staff of the Clinical Research Center of the FOB/USP. The authors are gratefull to Mrs. Larissa Tercilia Grizzo for technical support with proteomic analysis.

Funding

The authors thank FAPESP for financial support and for the concession of a scholarship to the first (Proc. FAPESP 2017/05031-2) and second (Proc. FAPESP 2018/17860-6) authors. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001.

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Authors and Affiliations

  1. Department of Biological Sciences - Discipline of Biochemistry, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisolla, 9-75, Bauru, SP, 17012-90, Brazil

    Talita Mendes Oliveira Ventura, Nathalia Regina Ribeiro, Even Akemi Taira, Aline de Lima Leite, Aline Dionizio & Marília Afonso Rabelo Buzalaf

  2. Department of Surgery, Stomatology, Pathology and Radiology - Discipline of Radiology and Stomatology, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisolla, 9-75, Bauru, SP, 17012-90, Brazil

    Cássia Maria Fischer Rubira & Paulo Sérgio da Silva Santos

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  1. Talita Mendes Oliveira Ventura
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  2. Nathalia Regina Ribeiro
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  8. Marília Afonso Rabelo Buzalaf
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Correspondence to Marília Afonso Rabelo Buzalaf.

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Ethical approval

The collection of the samples started after approval by the local Institutional Ethics Committee (No. 61484116.0.0000.5417), Bauru School of Dentistry, University of São Paulo, and signature of informed consent. The study was performed in accordance with the Declaration of Helsinki.

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Ventura, T.M.O., Ribeiro, N.R., Taira, E.A. et al. Radiotherapy changes the salivary proteome in head and neck cancer patients: evaluation before, during, and after treatment. Clin Oral Invest 26, 225–258 (2022). https://doi.org/10.1007/s00784-021-03995-5

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