Antunes Heliton S, Wajnberg Gabriel, Pinho Marcos B, Jorge Natasha Andressa Nogueira, de Moraes Joyce Luana Melo, Stefanoff Claudio Gustavo, Herchenhorn Daniel, Araújo Carlos M M, Viégas Celia Maria Pais, Rampini Mariana P, Dias Fernando L, de Araujo-Souza Patricia Savio, Passetti Fabio, Ferreira Carlos G
Clinical Research Division, Instituto Nacional de Câncer (INCA), Rua André Cavalcante, n 37, 2 andar, Rio de Janeiro, RJ, 20231-050, Brazil.
Bioinformatics Unit, Clinical Research Coordination, Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil.
Lasers Med Sci. 2018 Jan;33(1):11-18. doi: 10.1007/s10103-017-2313-8. Epub 2017 Aug 24.
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.
口腔黏膜炎是头颈部鳞状细胞癌患者接受放化疗时发生的一种急性毒性反应。在本研究中，我们评估了接受光生物调节疗法治疗的患者口腔黏膜角质形成细胞中的基因表达差异，并试图将分子机制与临床发现联系起来。2009年6月至2010年12月，27例患者纳入一项随机双盲试点研究。在放化疗的第1天和第10天采集13例患者的颊黏膜涂片，通过互补DNA（cDNA）微阵列分析这两个日期样本的整体基因表达。此外，还在放化疗的第1天（D1）和第10天（D10）采集另外14例患者的样本，用于随后通过定量聚合酶链反应（qPCR）验证cDNA微阵列的结果。与对照组相比，表达阵列分析在我们的治疗后样本中鉴定出105个上调基因和60个下调基因。在变化倍数最高的上调基因中，有趣的是观察到与角质形成细胞分化相关的基因。在下调基因中观察到与细胞毒性和免疫反应相关的基因。结果表明，在激光治疗组中，已知在人表皮角质形成细胞分化过程中被诱导的基因上调，而与细胞毒性和免疫反应相关的基因下调。这些结果支持了先前的临床发现，即与光生物调节疗法相关的口腔黏膜炎发生率较低可能与参与角质形成细胞分化的基因激活有关。
