Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192 Japan.
Department of Regenerative and Infectious Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Clin Epigenetics. 2017 Jun 12;9:64. doi: 10.1186/s13148-017-0363-1. eCollection 2017.
This study examined ( methylation profiles of head and neck cancer (HNSCC) patients at diagnosis and follow-up and evaluated their prognostic significance and value as a biomarker. expression was examined in a panel of cell lines by quantitative reverse transcription polymerase chain reaction (RT-PCR). The methylation status of the promoter was examined by quantitative methylation-specific PCR.
promoter methylation was associated with transcriptional inhibition and was correlated with disease recurrence in 64.8% of cases, with an odds ratio of 1.914 (95% confidence interval: 1.157-3.164; = 0.011) by multivariate Cox proportional hazard regression analysis. promoter hypermethylation showed highly discriminatory receiver operator characteristic curve profiles that clearly distinguished HNSCC from adjacent normal mucosal tissue, and was correlated with reduced disease-free survival (DFS) (log-rank test, = 0.01). Hypermethylation of tumor-related genes was higher among patients with methylation than among those without methylation ( < 0.001). Furthermore, hypermethylation was associated with expression of , , and genes.
This study suggests that CpG hypermethylation is a likely mechanism of gene inactivation, supporting the hypothesis that the gene may play a role in the tumorigenesis of HNSCC and may serve as an important biomarker.
本研究检测了头颈部癌症(HNSCC)患者在诊断和随访时的甲基化谱,并评估了其作为生物标志物的预后意义和价值。通过定量逆转录聚合酶链反应(RT-PCR)检测细胞系中 的表达。通过定量甲基化特异性 PCR 检测 的启动子甲基化状态。
启动子甲基化与转录抑制有关,与 64.8%的病例的疾病复发相关,多变量 Cox 比例风险回归分析的优势比为 1.914(95%置信区间:1.157-3.164;=0.011)。 启动子高甲基化显示出高度区分的接收者操作特征曲线谱,可清楚地区分 HNSCC 与相邻正常黏膜组织,并与降低无病生存率(DFS)相关(对数秩检验,=0.01)。与无甲基化的患者相比,发生 甲基化的患者中肿瘤相关基因的甲基化率更高(<0.001)。此外, 甲基化与 、 和 基因的表达相关。
本研究表明,CpG 高甲基化可能是 基因失活的一种机制,支持 基因可能在 HNSCC 的肿瘤发生中发挥作用,并可能作为一个重要的生物标志物的假说。