甲基化与转录组学的综合分析为头颈部鳞状细胞癌的诊断、预后和免疫特征鉴定了一种新的风险模型。

Integrated analysis of methylation and transcriptome identifies a novel risk model for diagnosis, prognosis, and immune characteristics in head and neck squamous cell carcinoma.

机构信息

Department of Otorhinolaryngology of Longgang Center Hospital, the Ninth People's Hospital of Shenzhen, Shenzhen, 518116, China.

Department of Gastroenterology of Longgang Center Hospital, the Ninth People's Hospital of Shenzhen, Shenzhen, 518116, China.

出版信息

Mol Genet Genomics. 2024 Jul 20;299(1):71. doi: 10.1007/s00438-024-02164-z.

DOI:10.1007/s00438-024-02164-z

PMID:39031208

Abstract

BACKGROUND

DNA methylation is an important epigenetic modification that plays a crucial role in the development and progression of various tumors. However, the association between methylation‑driven genes and diagnosis, prognosis, and immune characteristics of head and neck squamous cell carcinoma (HNSCC) remains unclear.

METHODS

We obtained transcriptome, methylation, and clinical data from HNSCC patients in TCGA database, and used MethylMix algorithm to identify methylation-driven genes. A methylation driven gene-related risk model was constructed using Lasso regression analysis, and validated using data from GEO database. Immune infiltration and immune function analysis of the expression profiles were conducted using ssGSEA. Differences in immune checkpoint-related genes were analyzed, and the efficacy of immunotherapy was evaluated using TCIA database. Finally, a series of cell functional experiments were conducted to validate the results.

RESULTS

Five methylation-driven genes were identified and utilized to construct a prognostic risk model. Based on the median risk score, all patients were categorized into high-risk and low-risk groups. The K-M analysis revealed that patients in the high-risk group have a worse prognosis. Additionally, the risk model demonstrated better prognostic predictive value as indicated by ROC analysis. GSEA enrichment analysis indicated that gene sets in the high and low-risk groups were primarily enriched in pathways associated with tumor immunity and metabolism. Our subsequent investigations showed that high-risk patients exhibited more immunosuppressive phenotypes, while low-risk patients were more likely to respond positively to immunotherapy.

CONCLUSION

These findings of our research have the potential to improve patient stratification, guide treatment decisions, and advance the development of personalized therapies for HNSCC.

摘要

背景

DNA 甲基化是一种重要的表观遗传修饰，在各种肿瘤的发生和发展中起着至关重要的作用。然而，甲基化驱动基因与头颈部鳞状细胞癌（HNSCC）的诊断、预后和免疫特征之间的关联尚不清楚。

方法

我们从 TCGA 数据库中获取了 HNSCC 患者的转录组、甲基化和临床数据，并使用 MethylMix 算法来识别甲基化驱动基因。使用 Lasso 回归分析构建了一个甲基化驱动基因相关的风险模型，并使用 GEO 数据库的数据进行了验证。使用 ssGSEA 对表达谱进行免疫浸润和免疫功能分析。分析免疫检查点相关基因的差异，并使用 TCIA 数据库评估免疫治疗的疗效。最后，进行了一系列细胞功能实验来验证结果。

结果

鉴定了 5 个甲基化驱动基因，并用于构建预后风险模型。根据中位数风险评分，将所有患者分为高风险和低风险组。K-M 分析表明，高风险组患者的预后较差。此外，ROC 分析表明，该风险模型具有更好的预后预测价值。GSEA 富集分析表明，高低风险组的基因集主要富集在与肿瘤免疫和代谢相关的途径中。我们随后的研究表明，高风险患者表现出更多的免疫抑制表型，而低风险患者更有可能对免疫治疗产生积极反应。