Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, Sichuan 610041, P.R. China.
Mol Med Rep. 2019 Jul;20(1):622-632. doi: 10.3892/mmr.2019.10294. Epub 2019 May 24.
Head and neck squamous cell carcinoma (HNSCC) remains one of the most common malignancies associated with poor prognosis. DNA methylation has emerged as an important mechanism underlying the radio‑resistance of tumors. Prognostic biomarkers based on radiotherapy‑related aberrant DNA methylation are limited. Methylation profiles of 388 patients with HNSCC were acquired from The Cancer Genome Atlas (TCGA) portal. Genes with differentially methylated CpG sites (DMGs) were screened between patients with a favorable and poor prognosis with or without radiotherapy. A weight gene co‑methylation network was constructed using a Weighted Gene Co‑expression Network Analysis (WGCNA) package. A lasso Cox‑PH model was used to identify the optimal panel of genes with the ability to predict survival in these patients. Prognostic performance of the multi‑gene methylation signature was assessed in a training set and confirmed in a validation set. A total of 976 DMGs were observed between favorable and poor prognostic samples. Four DMG‑enriched co‑methylation modules were identified. A four‑gene methylation signature was determined by the lasso Cox‑PH model that consisted of ZNF10, TMPRSS12, ERGIC2, and RNF215. The risk score based on the four‑gene signature was able to divide the training or validation set into two risk groups with significantly different overall survival. Thus, the present study revealed a radiotherapy‑related four‑gene methylation signature to predict survival outcomes of patients with HNSCC, providing candidate therapeutic targets for novel therapy against HNSCC. However, substantial validation experiments are required.
头颈部鳞状细胞癌（HNSCC）仍然是预后不良的最常见恶性肿瘤之一。DNA 甲基化已成为肿瘤放射抵抗的重要机制。基于放疗相关异常 DNA 甲基化的预后生物标志物有限。从癌症基因组图谱（TCGA）门户网站获得了 388 例 HNSCC 患者的甲基化谱。在有或没有放疗的情况下，筛选了预后良好和预后不良患者之间具有差异甲基化 CpG 位点（DMGs）的基因。使用加权基因共表达网络分析（WGCNA）包构建了加权基因共甲基化网络。使用lasso Cox-PH 模型来识别具有预测这些患者生存能力的最佳基因组合。多基因甲基化特征的预后性能在训练集中进行评估，并在验证集中得到证实。在预后良好和预后不良的样本之间观察到 976 个 DMGs。确定了四个 DMG 富集的共甲基化模块。lasso Cox-PH 模型确定了由 ZNF10、TMPRSS12、ERGIC2 和 RNF215 组成的四基因甲基化特征。基于四个基因特征的风险评分能够将训练或验证集分为两个具有显著不同总生存的风险组。因此，本研究揭示了一种与放疗相关的四基因甲基化特征，可预测 HNSCC 患者的生存结果，为针对 HNSCC 的新型治疗提供了候选治疗靶点。然而，需要进行大量验证实验。
