缺乏基质依赖性细胞死亡（Anoikis）是一种程序性细胞死亡方式，在个体的正常发育和稳态中起着至关重要的作用，并在癌症的发生和发展中发挥重要作用。本研究的作者们旨在建立与Anoikis相关的基因签名，以预测头颈鳞状细胞癌（HNSCC）患者的治疗效果和预后。从公共数据库检索了HNSCC患者中与Anoikis相关基因的转录组数据，以辅助形成这一基因签名。使用最小绝对收缩和选择算子回归和Cox回归分析的组合方法创建了一种新的与Anoikis相关基因签名。利用单细胞分析探索了HNSCC肿瘤免疫微环境与ARGs之间的关系。根据风险评分的中位数将HNSCC患者分为高风险组和低风险组。研究还调查了低风险组和高风险组之间的免疫细胞浸润状态的变化、肿瘤微环境、对免疫治疗和化疗的敏感性以及功能富集。共有18个ARGs纳入了签名的制定中。通过多变量Cox回归分析和Kaplan-Meier生存分析验证了我们的签名作为独立预测指标的有效性。总体而言，高风险患者的预后更差。低风险组的患者预后更好，并对联合免疫治疗有更好的反应，免疫评分和活性水平更高，并且有更多的免疫细胞浸润。此外，基因集富集分析结果显示，低风险组在几个与免疫相关的通路中表现出更高的活性。然而，高风险患者对化疗的反应较好。本研究旨在开发一种新的ARG签名，以预测HNSCC患者的预后和对免疫和化疗方案的敏感性，从而推动为HNSCC患者开发新的化疗和免疫治疗方法。版权所有 © 2023 作者。由Wolters Kluwer Health, Inc.出版。

Anoikis, a mode of programmed cell death, is essential for normal development and homeostasis in the organism and plays an important role in the onset and progression of cancers. The authors of this research sought to establish a gene signature associated with anoikis to predict therapy outcomes and patient prognosis for individuals with head and neck squamous cell carcinoma (HNSCC). Transcriptome data of anoikis-related genes (ARGs) in individuals with HNSCC were retrieved from public databases to aid in the formulation of the gene signature. A novel ARG signature was then created using a combination of the Least Absolute Shrinkage and Selection Operator regression and Cox regression analysis. The relationship between ARGs and tumor immune microenvironment in HNSCC was explored using single-cell analysis. HNSCC individuals were classified into high-risk and low-risk groups as per the median value of risk score. The study also investigated the variations in the infiltration status of immune cells, tumor microenvironment, sensitivity to immunotherapy and chemotherapeutics, as well as functional enrichment between the low-risk and high-risk categories. A total of 18 ARGs were incorporated in the formulation of the signature. Our signature's validity as a standalone predictive predictor was validated by multivariate Cox regression analysis and Kaplan-Meier survival analysis. Generally, the prognosis was worse for high-risk individuals. Subjects in the low-risk groups had a better prognosis and responded in a better way to combination immunotherapy, had higher immunological ratings and activity levels, and had more immune cell infiltration. In addition, gene set enrichment analysis findings showed that the low-risk subjects exhibited heightened activity in several immune-related pathways. However, the high-risk patients responded better to chemotherapy. The aim of this research was to develop a new ARG signature to predict the prognosis and sensitivity to immunotherapeutic and chemotherapeutic schemes for HNSCC patient. As a result, this could help spur the creation of new chemotherapeutics and immunotherapeutic approaches for patients with HNSCC.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.