Division of Molecular Medicine, Ruđer Bošković Institute, 10000 Zagreb, Croatia.
Department of Maxillofacial Surgery, School of Medicine, Clinical Hospital Dubrava, University of Zagreb, 10000 Zagreb, Croatia.
Int J Mol Sci. 2020 Sep 18;21(18):6853. doi: 10.3390/ijms21186853.
There is a strong need to find new, good biomarkers of head and neck squamous cell carcinoma (HNSCC) because of the bad prognoses and high mortality rates. The aim of this study was to identify the potential biomarkers in HNSCC that have differences in their DNA methylome and potentially premalignant oral lesions, in comparison to healthy oral mucosa. In this study, 32 oral samples were tested: nine healthy oral mucosae, 13 HNSCC, and 10 oral lesions for DNA methylation by the Infinium MethylationEPIC BeadChip. Our findings showed that a panel of genes significantly hypermethylated in their promoters or specific sites in HNSCC samples in comparison to healthy oral samples, which are mainly oncogenes, receptor, and transcription factor genes, or genes included in cell cycle, transformation, apoptosis, and autophagy. A group of hypomethylated genes in HNSCC, in comparison to healthy oral mucosa, are mainly involved in the host immune response and transcriptional regulation. The results also showed significant differences in gene methylation between HNSCC and potentially premalignant oral lesions, as well as differently methylated genes that discriminate between oral lesions and healthy mucosa. The given methylation panels point to novel potential biomarkers for early diagnostics of HNSCC, as well as potentially premalignant oral lesions.
由于头颈部鳞状细胞癌(HNSCC)的预后较差和死亡率较高,因此强烈需要寻找新的、良好的生物标志物。本研究旨在确定与健康口腔黏膜相比,在 HNSCC 中存在差异的 DNA 甲基化组学和潜在的癌前口腔病变的潜在生物标志物。在这项研究中,测试了 32 个口腔样本:9 个健康口腔黏膜、13 个 HNSCC 和 10 个口腔病变的 DNA 甲基化通过 Infinium MethylationEPIC BeadChip。我们的研究结果表明,一组在 HNSCC 样本中与健康口腔样本相比在启动子或特定部位显著高甲基化的基因,主要是癌基因、受体和转录因子基因,或参与细胞周期、转化、凋亡和自噬的基因。与健康口腔黏膜相比,HNSCC 中一组低甲基化的基因主要参与宿主免疫反应和转录调控。结果还显示 HNSCC 与潜在癌前口腔病变之间的基因甲基化存在显著差异,以及区分口腔病变和健康黏膜的差异甲基化基因。所提供的甲基化谱指出了用于 HNSCC 早期诊断以及潜在癌前口腔病变的新的潜在生物标志物。