Tian Xudong, Shi Congyu, Liu Shan, Zhao Chengzhi, Wang Xiaoyi, Cao Yubin
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.
Department of Head and Neck Oncology, West China College of Stomatology, Sichuan University, Chengdu, China.
J Dent Sci. 2023 Jan;18(1):57-64. doi: 10.1016/j.jds.2022.07.010. Epub 2022 Aug 5.
BACKGROUND/PURPOSE: 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 , , , , , , , , and . The risk score was a significant prognostic factor both in training ( < 0.001) and validation dataset (GSE65858: = 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 + T cells, activated + 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 , and .
The mrDEGs can stratify HNSCC patients' prognosis, which correlates with alterations in tumor immune infiltrations and immune checkpoints.
背景/目的：甲基化组分析可能有助于对头颈部鳞状细胞癌（HNSCC）患者进行预后分层。本研究旨在鉴定甲基化相关差异表达基因（mrDEGs），并评估其在预测HNSCC患者生存、肿瘤免疫微环境改变和免疫检查点方面的效能。
来自TCGA数据库的528例HNSCC和50例正常样本的甲基化组和转录组数据用作训练队列。我们鉴定了mrDEGs，并使用Kaplan-Meier分析和多变量Cox回归构建了风险评分模型。在GSE65858和GSE41613中验证了风险评分的预后效能。我们确定了mrDEGs先前定义的生物学过程的富集情况。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的表达。
风险评分模型由9个预后mrDEGs构成，包括 ， ， ， ， ， ， ， ，和 。风险评分在训练集（ < 0.001）和验证数据集（GSE65858： = 0.008；GSE41613 = 0.015）中都是一个显著的预后因素。预后mrDEGs在多个免疫相关途径中富集。低风险患者中效应免疫细胞增加，包括 + T细胞、活化的 + T细胞和浆细胞，而高风险组中募集了肿瘤相关M2巨噬细胞。免疫检查点的表达在低风险患者中通常更高，包括 ， 和 。
mrDEGs可对HNSCC患者的预后进行分层，这与肿瘤免疫浸润和免疫检查点的改变相关。
