Mucositis in patients with tonsil squamous cell carcinoma: gene expression profile of oral mucosa before, during, and after radiation therapy

Objectives: In patients with tonsil squamous cell cancer (TSCC), radiation-therapy (RT) induce mucositis, which is clinically challenging with limited prophylactic interventions and no predictive tests. In a pilot study set-up, we performed global gene-expression analysis on human oral mucosa tissue and blood cells to identify differential expressed genes involved in mucositis pathogenesis. Materials and Methods: Eight patients with TSCC had consecutive buccal biopsies and blood samples taken before, after 7 days of RT, and 20 days following RT. We monitored clinical mucositis and applied gene-expression analysis to the tissues. Single biopsies and blood tests from 9 healthy individuals served as controls (CON). Results: In response to RT, we did not register changes in the blood cells, but we found upregulation of both apoptosis inducers and inhibitors in the mucosa: EDA2R and MDM2; and POLH, encoding a polymerase that replicates UV-damaged DNA. Six members of the histone cluster family, e.g., HIST1H3B, involved in nucleosome structure, were downregulated. Genes related to proliferation were also altered: MKI67 (downregulated), encoding Ki-67-proliferation; and KRT16 (upregulated), encoding keratin16, characteristic in early differentiated epithelial cells. None of these alterations were associated to mucositis severity. However, before treatment, LY6G6C, which encodes a surface immunoregulatory protein, was upregulated in NM compared to UM, although not significantly. Conclusion: RT caused divergent changes in genes expression related to DNA damage and proliferation, all independently altered of mucositis severity. LY6G6C may be a potential predictive biomarker for UM following RT. Based on these result, we will design a prospective clinical validation trial, including more patients. Consecutive mucosa biopsies from 8 patients with tonsil squamous cell carcinoma one biopsy and blood test before radiotherapy (RT), one biopsy and blood test after 5 days of RT (2 Gy each day) and three weeks after the last exposure to RT