oral mucosa tissue gene expression profiling before, during, and after radiation therapy for tonsil squamous cell carcinoma.

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ID: 147916
2018
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Abstract
BACKGROUND:Radiation-therapy (RT) induces mucositis, a clinically challenging condition with limited prophylactic interventions and no predictive tests. In this pilot study, we applied global gene-expression analysis on serial human oral mucosa tissue and blood cells from patients with tonsil squamous cell cancer (TSCC) to identify genes involved in mucositis pathogenesis. METHODS AND FINDINGS:Eight patients with TSCC each provided consecutive buccal biopsies and blood cells before, after 7 days of RT treatment, and 20 days following RT. We monitored clinical mucositis and performed gene-expression analysis on tissue samples. We obtained control tissue from nine healthy individuals. After RT, expression was upregulated in apoptosis inducer and inhibitor genes, EDA2R and MDM2, and in POLH, a DNA-repair polymerase. Expression was downregulated in six members of the histone cluster family, e.g., HIST1H3B. Gene expression related to proliferation and differentiation was altered, including MKI67 (downregulated), which encodes the Ki-67-proliferation marker, and KRT16 (upregulated), which encodes keratin16. These alterations were not associated with the clinical mucositis grade. However, the expression of LY6G6C, which encodes a surface immunoregulatory protein, was upregulated before treatment in three cases of clinical none/mild mucositis, but not in four cases of ulcerative mucositis. CONCLUSION:RT caused molecular changes related to apoptosis, DNA-damage, DNA-repair, and proliferation without a correlation to the severity of clinical mucositis. LY6G6C may be a potential protective biomarker for ulcerative mucositis. Based on these results, our study model of consecutive human biopsies will be useful in designing a prospective clinical validation trial to characterize molecular mucositis and identify predictive biomarkers.
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marcussen2018plosoral Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Mette Marcussen;Mads Sønderkær;Julie Støve Bødker;Maria Andersen;Søren Nielsen;Charles Vesteghem;Ilse Christiansen;Olav Jonas Bergmann;Martin Bøgsted;Karen Dybkær;Mogens Vyberg;Hans Erik Johnsen
Journal ensaio pesquisa em educação em ciências
Year 2018
DOI
10.1371/journal.pone.0190709
URL
https://doi.org/10.1371/journal.pone.0190709
Keywords
medicinescience

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