Ferroptosis-associated DNA methylation signature predicts overall survival in patients with head and neck squamous cell carcinoma.
Ferroptosis-associated DNA methylation signature predicts overall survival in patients with head and neck squamous cell carcinoma.
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铁死亡相关的 DNA 甲基化特征可预测头颈鳞状细胞癌患者的总体生存率
DOI：
10.1186/s12864-022-08296-z
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发表时间：
2022-01-18
期刊：
影响因子：
4.4
通讯作者：
Liang J
中科院分区：
文献类型：
--
作者：
Xu Y;Hong M;Kong D;Deng J;Zhong Z;Liang J
背景头颈部鳞状细胞癌（HNSCC）是一种诊断晚、预后差的常见癌症。本研究的目的是鉴定一种新的与铁凋亡相关的DNA甲基化特征，作为HNSCC患者的替代诊断指标。方法从癌症基因组图谱（TCGA）中获取499例HNSCC患者的甲基组和转录组数据，其中口腔鳞状细胞癌（OSCC） 275例。另外一个独立的甲基化数据集来自NCBI基因表达综合数据库（GEO），其中包括50名OSCC患者。作为铁下垂活性的指标，每位患者的铁下垂评分（FS）是通过单样本基因集富集分析从转录组数据推断出来的。采用单因素、多因素和LASSO Cox回归分析选择CpG位点，构建与铁中毒相关的DNA甲基化特征，用于诊断患者。结果我们初步推断了每个TCGA HNSCC患者的FS，并将样本分为高FS和低FS亚组。结果显示，高fs亚组总生存期较差。此外，在两个HNSCC亚组之间鉴定了378个差异甲基化CpG位点（DMCs），其中16个被选择构建16个dna甲基化特征，用于使用LASSO和多变量Cox回归模型预测HNSCC患者的风险。相对工作特征（ROC）曲线分析显示，使用16-DNA甲基化特征对1年、3年和5年HNSCC生存具有很高的预测效率。在TCGA和GEO数据库的OSCC患者中也观察到其预测效率。此外，我们发现该特征与肿瘤免疫微环境（TIME）中免疫类型的分数相关，表明铁上塌和TIME在HNSCC进展中可能存在相互作用。结论：我们建立了一种新的与铁凋亡相关的16-DNA甲基化特征，可作为预测HNSCC（包括OSCC）患者预后结果的替代工具。
BackgroundHead and neck squamous cell carcinoma (HNSCC) is a common cancer characterized by late diagnosis and poor prognosis. The aim of this study was to identify a novel ferroptosis-related DNA methylation signature as an alternative diagnosis index for patients with HNSCC.MethodsMethylome and transcriptome data of 499 HNSCC patients, including 275 oral squamous cell carcinoma (OSCC) samples, were obtained from The Cancer Genome Atlas (TCGA). An additional independent methylation dataset of 50 OSCC patients from the NCBI Gene Expression Omnibus (GEO) database was used for validation. As an index of ferroptosis activity, the ferroptosis score (FS) of each patient was inferred from the transcriptome data using single-sample gene set enrichment analysis. Univariate, multivariate, and LASSO Cox regression analyses were used to select CpG sites for the construction of a ferroptosis-related DNA methylation signature for diagnosis of patients.ResultsWe initially inferred the FS of each TCGA HNSCC patient and divided the samples into high- and low-FS subgroups. Results showed that the high-FS subgroup displayed poor overall survival. Moreover, 378 differentially methylated CpG sites (DMCs) were identified between the two HNSCC subgroups, with 16 selected to construct a 16-DNA methylation signature for risk prediction in HNSCC patients using the LASSO and multivariate Cox regression models. Relative operating characteristic (ROC) curve analysis showed great predictive efficiency for 1-, 3-, and 5-year HNSCC survival using the 16-DNA methylation signature. Its predictive efficiency was also observed in OSCC patients from the TCGA and GEO databases. In addition, we found that the signature was associated with the fractions of immune types in the tumor immune microenvironment (TIME), suggesting potential interactions between ferroptosis and TIME in HNSCC progression.ConclusionsWe established a novel ferroptosis-related 16-DNA methylation signature that could be applied as an alternative tool to predict prognosis outcome in patients with HNSCC, including OSCC.
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