甲基化谱分析可能使头颈部鳞状细胞癌（HNSCC）患者的预后分层成为可能。本研究旨在确定与甲基化相关的差异表达基因（mrDEGs），并评估它们在预测HNSCC患者的生存率、肿瘤免疫微环境变化和免疫检查点方面的有效性。我们采用来自TCGA数据库的528个HNSCC患者和50个正常样本的甲基化组和转录组数据作为训练集。我们确定了mrDEGs并用Kaplan-Meier分析和多变量Cox回归构建了风险评分模型。风险评分的预后有效性在GSE65858和GSE41613中得到了验证。我们确定了mrDEGs先前定义的生物学过程的富集。我们将HNSCC患者分为低风险和高风险组，并比较了它们的免疫细胞浸润和免疫检查点表达。风险评分模型是由九个预后mrDEGs组成的，包括LIMD2、SYCP2、EPHX3、UCLH1、STC2、PRAME、SLC7A4、PLOD2和ACADL。风险评分既在训练（p <0.001）又在验证数据集中（GSE65858：P = 0.008；GSE41613 = 0.015）是一个重要的预后因子。预后mrDEGs在多种免疫相关途径中富集。低风险患者的效应器免疫细胞增加，包括CD8 + T细胞、激活的CD4 + T细胞和浆细胞，而肿瘤相关M2型巨噬细胞则在高风险组中被招募。低风险患者的免疫检查点表达通常较高，包括CTLA-4、PD-1和LAG3。 mrDEGs可以将HNSCC患者的预后分层，这与肿瘤免疫浸润和免疫检查点的变化有关。©2022中华民国牙科科学协会。Elsevier B.V.提供出版服务。

Analysis of methylomes may enable prognostic stratification in patients with head and neck squamous cell carcinoma (HNSCC). This study aimed to identify methylation-related differentially expressed genes (mrDEGs), and to assess their efficacy in predicting patients' survival, tumor immune microenvironment alterations and immune checkpoints in patients with HNSCC.The methylome and transcriptome data of 528 HNSCC and 50 normal samples from TCGA database were used as training cohort. We identified mrDEGs and constituted a risk score model using Kaplan-Meier analysis and multivariate Cox regression. The prognostic efficacy of the risk score was validated in GSE65858 and GSE41613. We determined the enrichment of previously defined biological processes of mrDEGs. We separated the HNSCC patients into low-risk and high-risk groups and compared their immune cell infiltration and immune checkpoints' expressions.The risk score model was constituted by nine prognostic mrDEGs, including LIMD2, SYCP2, EPHX3, UCLH1, STC2, PRAME, SLC7A4, PLOD2, and ACADL. The risk score was a significant prognostic factor both in training (P < 0.001) and validation dataset (GSE65858: P = 0.008; GSE41613 = 0.015). The prognostic mrDEGs were enriched in multiple immune-associated pathways. Effector immune cells were increased in low-risk patients, including CD8+ T cells, activated CD4+ T cells, and plasma cells, whereas tumor associated M2 macrophages were recruited in the high-risk group. Expressions of immune checkpoints were generally higher in low-risk patients, including CTLA-4, PD-1 and LAG3.The mrDEGs can stratify HNSCC patients' prognosis, which correlates with alterations in tumor immune infiltrations and immune checkpoints.© 2022 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.