Zhang Wei, Qu Mei, Yin Chun, Jin Zhiliang, Hu Ya
Department of Oncology, Jingzhou Hospital, Yangtze University, Jingzhou, China.
Department of Pharmacology, Health Science Center, Yangtze University, 1 Nanhuan Road, Jingzhou, 434023, Hubei, China.
Discov Oncol. 2024 Mar 2;15(1):56. doi: 10.1007/s12672-024-00921-5.
T cell exhaustion (TEX) signifies a condition of T cell disorder which implicate the therapeutic benefits and prognostic significance in patients with cancer. However, its role in the Head and Neck Squamous Carcinoma (HNSCC) remains incompletely understood.
The detailed data of HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) database and two Gene Expression Omnibus (GEO) datasets. We computed the expression scores of four TEX-related pathways and detected gene modules closely linked to these pathways, indicating prognostic significance. Following this, regression analyses were performed to select eight genes for the development of a predictive signature. The predictive capacity of this signature was evaluated. Additionally, we examined the relationships between TEX-related signature risk scores and the effectiveness of immunotherapy as well as drug sensitivity.
A novel prognostic model, comprising eight TEX-related genes, was established for patients with HNSCC. The prognostic value was further confirmed using additional GEO datasets: GSE65858 and GSE27020. This signature enables the stratification of patients into high- and low- risk groups, each showing distinct survival outcomes and responsiveness to immunotherapy. The low-risk group demonstrated improved prognosis and enhanced efficacy of immunotherapy. In addition, AZD6482, TAF1, Ribociclib, LGK974, PF4708671 and other drugs showed increased sensitivity in the high-risk group based on drug sensitivity values, offering tailored therapeutic recommendations for individuals with various risks profiles.
In conclusion, we developed a novel T cell exhaustion-associated signature, which holds considerable predictive value for both the prognosis of patients with HNSCC and the effectiveness of tumor immunotherapy.
T细胞耗竭（TEX）是一种T细胞功能紊乱状态，对癌症患者的治疗益处和预后具有重要意义。然而，其在头颈部鳞状细胞癌（HNSCC）中的作用仍未完全明确。
从癌症基因组图谱（TCGA）数据库和两个基因表达综合数据库（GEO）中获取HNSCC样本的详细数据。我们计算了四条与TEX相关通路的表达分数，并检测了与这些通路密切相关的基因模块，以评估其预后意义。随后，进行回归分析以选择八个基因用于构建预测模型。评估了该模型的预测能力。此外，我们还研究了TEX相关特征风险评分与免疫治疗效果以及药物敏感性之间的关系。
为HNSCC患者建立了一个包含八个与TEX相关基因的新型预后模型。使用另外两个GEO数据集GSE65858和GSE27020进一步证实了该模型的预后价值。该模型能够将患者分为高风险和低风险组，两组具有不同的生存结果和对免疫治疗的反应。低风险组显示出更好的预后和更高的免疫治疗疗效。此外，根据药物敏感性值，AZD6482、TAF1、Ribociclib、LGK974、PF4708671等药物在高风险组中显示出更高的敏感性，为不同风险特征的个体提供了个性化的治疗建议。
总之，我们开发了一种新型的与T细胞耗竭相关的特征模型，该模型对HNSCC患者的预后和肿瘤免疫治疗效果具有重要的预测价值。
