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cDNA microarray analysis of human keratinocytes cells of patients submitted to chemoradiotherapy and oral photobiomodulation therapy: pilot study

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Abstract

Oral mucositis is an acute toxicity that occurs in patients submitted to chemoradiotherapy to treat head and neck squamous cell carcinoma. In this study, we evaluated differences in gene expression in the keratinocytes of the oral mucosa of patients treated with photobiomodulation therapy and tried to associate the molecular mechanisms with clinical findings. From June 2009 to December 2010, 27 patients were included in a randomized double-blind pilot study. Buccal smears from 13 patients were obtained at days 1 and 10 of chemoradiotherapy, and overall gene expression of samples from both dates were analyzed by complementary DNA (cDNA) microarray. In addition, samples from other 14 patients were also collected at D1 and D10 of chemoradiotherapy for subsequent validation of cDNA microarray findings by qPCR. The expression array analysis identified 105 upregulated and 60 downregulated genes in our post-treatment samples when compared with controls. Among the upregulated genes with the highest fold change, it was interesting to observe the presence of genes related to keratinocyte differentiation. Among downregulated genes were observed genes related to cytotoxicity and immune response. The results indicate that genes known to be induced during differentiation of human epidermal keratinocytes were upregulated while genes associated with cytotoxicity and immune response were downregulated in the laser group. These results support previous clinical findings indicating that the lower incidence of oral mucositis associated with photobiomodulation therapy might be correlated to the activation of genes involved in keratinocyte differentiation.

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Acknowledgments

This work was supported by the National Cancer Institute, Brazil. The authors would like to thank the National Tumor Bank-INCA (BNT) for their support during the first stage of this work. F.P. is supported by the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). N.A.N.J and G.W. are supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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No outside funding was received for this study.

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Authors and Affiliations

  1. Clinical Research Division, Instituto Nacional de Câncer (INCA), Rua André Cavalcante, n 37, 2 andar, Rio de Janeiro, RJ, 20231-050, Brazil

    Heliton S. Antunes, Marcos B. Pinho, Joyce Luana Melo de Moraes, Claudio Gustavo Stefanoff & Mariana P. Rampini

  2. Bioinformatics Unit, Clinical Research Coordination, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil

    Gabriel Wajnberg, Natasha Andressa Nogueira Jorge & Fabio Passetti

  3. Head and Neck Oncology Group, Grupo de Oncologia D’Or, Rio de Janeiro, Brazil

    Gabriel Wajnberg, Natasha Andressa Nogueira Jorge, Daniel Herchenhorn & Fabio Passetti

  4. Radiation Oncology Division, INCA, Rio de Janeiro, Brazil

    Gabriel Wajnberg, Natasha Andressa Nogueira Jorge, Carlos M. M. Araújo, Celia Maria Pais Viégas & Fabio Passetti

  5. Head and Neck Surgery Division, INCA, Rio de Janeiro, Brazil

    Gabriel Wajnberg, Natasha Andressa Nogueira Jorge, Fernando L. Dias & Fabio Passetti

  6. Program of Cellular Biology, INCA, Rio de Janeiro, Brazil

    Gabriel Wajnberg, Natasha Andressa Nogueira Jorge, Patricia Savio de Araujo-Souza & Fabio Passetti

  7. Department of Immunobiology, Universidade Federal Fluminense (UFF), Niterói, Brazil

    Gabriel Wajnberg, Natasha Andressa Nogueira Jorge, Patricia Savio de Araujo-Souza & Fabio Passetti

  8. Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil

    Gabriel Wajnberg, Natasha Andressa Nogueira Jorge & Fabio Passetti

  9. D’Or Institute for Research and Education, Rio de Janeiro, Brazil

    Carlos G. Ferreira

Authors
  1. Heliton S. Antunes
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  2. Gabriel Wajnberg
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  3. Marcos B. Pinho
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  4. Natasha Andressa Nogueira Jorge
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  8. Carlos M. M. Araújo
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  9. Celia Maria Pais Viégas
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  11. Fernando L. Dias
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  14. Carlos G. Ferreira
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Corresponding author

Correspondence to Heliton S. Antunes.

Ethics declarations

The research protocol was initially submitted and approved by the Ethics Committee from the National Cancer Institute of Brazil (Protocol 17/07).

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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The authors declare that they have no conflict of interest.

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Antunes, H.S., Wajnberg, G., Pinho, M.B. et al. cDNA microarray analysis of human keratinocytes cells of patients submitted to chemoradiotherapy and oral photobiomodulation therapy: pilot study. Lasers Med Sci 33, 11–18 (2018). https://doi.org/10.1007/s10103-017-2313-8

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