已经确定了端粒酶功能失调作为多种癌症，包括头颈部鳞状细胞癌 (HNSCC) 进展的生物标志物。本研究旨在确定 HNSCC 的端粒酶维护基因 (TMG) 相关的预后和治疗反应特征。HNSCC 的转录组和临床数据分别来自癌症基因组图谱 (TCGA) 和 Gene Expression Omnibus 数据库。使用非负矩阵分解 (NMF) 来鉴定基于 TMG 的分子亚型，利用基因集富集分析 (GSEA) 来分析亚型之间的差异表达途径，并建立了一个基于 TMG 的风险评分模型。采用 Kaplan-Meier 生存分析评估亚组间预后特征，并评估 TMG 相关的分子亚型和风险评分模型与免疫浸润、免疫治疗和化疗敏感性之间的相关性。基于 59 个与 TMG 相关的基因，确定了两种 HNSCC 亚型，在预后、免疫细胞浸润和治疗反应方面存在显著的异质性。此外，还开发了一个由 9 个基因组成的 TMG 相关风险签名，用于评估 HNSCC 患者的预后。该签名对 HNSCC 预后具有显著的预测能力，与免疫细胞浸润和免疫治疗反应显著相关。构建了一个集成风险签名、N 分期和放疗的图谱来预测 HNSCC 患者的 1、3、5 年总生存期 (OS)，其性能优于其他预后模型，并包括基于 TMG 的风险评分、放疗和 N 分期。本研究确定了 HNSCC 中的 TMG 相关分子亚型，并开发了一种新的预后评分模型，突显了 TMG 在 HNSCC 预后和免疫治疗中的潜在价值。 版权所有 © 2023 作者。 Wolters Kluwer Health, Inc. 出版。

Telomere dysfunction has been identified as a biological marker of cancer progression in several types of cancer, including Head and Neck Squamous Cell Carcinoma (HNSCC). This study aimed to characterize the telomere maintenance genes (TMG)-related signature in prognosis and treatment response in HNSCC. The transcriptome and clinical data of HNSCC were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases, respectively. Non-negative matrix factorization (NMF) was used to identify molecular subtypes derived from TMG. Gene set enrichment analysis (GSEA) was performed to analyze the differentially expressed pathways between subtypes, and a risk score model derived from TMG was established. Kaplan-Meier survival analysis was used to evaluate inter-group prognostic features, and the correlation between TMG-derived molecular subtypes and risk score model with immune infiltration, immunotherapy, and chemosensitivity was assessed. Two HNSCC subtypes were identified based on 59 TMG-related genes, which exhibit significant heterogeneity in prognosis, immune cell infiltration, and treatment response. Additionally, a TMG-derived risk signature containing 9 genes was developed to assess the prognosis of HNSCC patients. The signature had significant predictive ability for HNSCC prognosis and was significantly correlated with immune cell infiltration and immunotherapy response. A nomogram integrating the risk signature, N stage and radiotherapy was constructed to predict 1-, 3-, and 5-year overall survival (OS) of HNSCC patients, which had better performance than other prognostic models and included TMG-derived risk score, radiotherapy, and N stage. This study identified TMG-derived molecular subtypes in HNSCC and developed a novel prognostic score model, highlighting the potential value of TMG in HNSCC prognosis and immunotherapy.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.