喉鳞状细胞癌（LSCCs）是具有高发病率的头颈鳞状细胞癌患者中的侵袭性肿瘤。Cuproptosis是一种影响肿瘤恶性和进展的程序性细胞死亡类型。本研究的目的是调查与Cuproptosis相关的长非编码RNA（crlncRNAs）与LSCC肿瘤免疫微环境和化疗药物敏感性之间的关系，以及crlncRNA对LSCC恶性的影响。从癌基因组图谱中检索患有LSCC的患者的临床和RNA测序数据。基于单变量Cox回归分析，确定了差异表达的与预后相关的crlncRNAs，使用LASSO Cox回归开发和验证LSCC的crlncRNA签名。最后，评估核心标志crlncRNA LINC02454在体外和体内对LSCC恶性进展的影响。我们确定了一个四个crlncRNA的签名（LINC02454，AC026310.1，AC090517.2和AC000123.1），根据该签名将患者分为高风险和低风险组。crlncRNA签名风险评分是整体和无进展生存的独立预后指标，并具有较高的预测准确性。具有更高浸润树突细胞、M0巨噬细胞和中性粒细胞丰度的患者预后较差，高风险组对多种化疗药物高度敏感。LINC02454的敲除通过诱导Cuproptosis抑制肿瘤。发现了一个由四个crlncRNAs组成的新型标志物签名，作为LSCC患者的风险预测模型具有高度准确性，并具有改善LSCC的诊断、预后和治疗的潜力。© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Laryngeal squamous cell carcinomas (LSCCs) are aggressive tumors with the second-highest morbidity rate in patients with head and neck squamous cell carcinoma. Cuproptosis is a type of programmed cell death that impacts tumor malignancy and progression. The purpose of this study was to investigate the relationship between cuproptosis-related long non-coding RNAs (crlncRNAs) and the tumor immune microenvironment and chemotherapeutic drug sensitivity in LSCC, and crlncRNA impact on LSCC malignancy.Clinical and RNA-sequencing data from patients with LSCC were retrieved from the Cancer Genome Atlas. Differentially expressed prognosis-related crlncRNAs were identified based on univariate Cox regression analysis, a crlncRNA signature for LSCC was developed and validated using LASSO Cox regression. Finally, the effect of LINC02454, the core signature crlncRNA, on LSCC malignancy progression was evaluated in vitro and in vivo.We identified a four-crlncRNA signature (LINC02454, AC026310.1, AC090517.2, and AC000123.1), according to which we divided the patients into high- and low-risk groups. The crlncRNA signature risk score was an independent prognostic indicator for overall and progression-free survival, and displayed high predictive accuracy. Patients with a higher abundance of infiltrating dendritic cells, M0 macrophages, and neutrophils had worse prognoses and those in the high-risk group were highly sensitive to multiple chemotherapeutic drugs. Knockdown of LINC02454 caused tumor suppression, via cuproptosis induction.A novel signature of four crlncRNAs was found to be highly accurate as a risk prediction model for patients with LSCC and to have potential for improving the diagnosis, prognosis, and treatment of LSCC.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.