Zhou Liuqing, Cheng Qing, Hu Yao, Tan Haoyue, Li Xiaoguang, Wu Shuhui, Zhou Tao, Zhou Jieyu
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Otorhinolaryngology, The Central Hospital of Wuhan, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2022 Dec 22;12:1030802. doi: 10.3389/fonc.2022.1030802. eCollection 2022.
Head and neck squamous cell carcinoma (HNSCC) is a malignant neoplasm typically induced by alcohol and tobacco consumption, ranked the sixth most prevalent cancer globally. This study aimed to establish a cuproptosis-related lncRNA predictive model to assess the clinical significance in HNSCC patients.
The Cancer Genome Atlas (TCGA) database was utilized to download cuproptosis-related genes, lncRNAs profiles, and selected clinical information of 482 HNSCC samples. Cuproptosis-related lncRNAs were analyzed by Pearson correlation method, with the least absolute shrinkage and selection operator (LASSO) and univariate/multivariate Cox analyses performed to establish the cuproptosis-related lncRNA predictive model. Subsequently, the time-dependent receiver operating characteristics (ROC) and Kaplan-Meier analysis were applied to assess its prediction ability, and the model was verified by a nomogram, univariate/multivariate Cox analysis, and calibration curves. Furthermore, the principal component analysis (PCA), immune analysis, and gene set enrichment analyses (GSEA) were performed, and the 50% inhibitory concentration (IC50) prediction in the risk groups was calculated. Furthermore, the expression of six cuproptosis-related lncRNAs in HNSCC and paracancerous tissues was detected by quantitative real-time PCR (qRT-PCR).
A total of 467 lncRNAs were screened as cuproptosis-associated lncRNAs in HNSCC tissues to establish an eight cuproptosis-related lncRNA prognostic signature consisting of AC024075.3, AC090587.2, AC116914.2, AL450384.2, CDKN2A-DT, FAM27E3, JPX, and LNC01089. For the high-risk group, the results demonstrated a satisfactory predicting performance with considerably worse overall survival (OS). Multivariate Cox regression confirmed that the risk score was a reliable predictive factor (95% CI: 1.089-1.208, hazard ratio =1.147), with the area of 1-, 3-, and 5-year OS under the ROC curve of 0.690, 0.78524, and 0.665, respectively. The differential analysis revealed that JPX was significantly upregulated in HNSCC tissues, while AC024075.3, AC090587.2, AC116914.2, AL450384.2, CDKN2A-DT were downregulated in HNSCC tissues by qRT-PCR assays. In addition, this gene signature was also associated with some immune-related pathways and immune cell infiltration and affected the anti-cancer immune response. Furthermore, Bexarotene, Bleomycin, Gemcitabine, etc., were identified as potential therapeutic compounds for HNSCC.
This novel cuproptosis-related lncRNAs prognostic signature could predict prognosis and help propose novel individual therapeutic targets for HNSCC.
头颈部鳞状细胞癌（HNSCC）是一种通常由饮酒和吸烟诱发的恶性肿瘤，在全球最常见癌症中排名第六。本研究旨在建立一种与铜死亡相关的lncRNA预测模型，以评估其在HNSCC患者中的临床意义。
利用癌症基因组图谱（TCGA）数据库下载482例HNSCC样本的铜死亡相关基因、lncRNA谱及选定的临床信息。采用Pearson相关法分析与铜死亡相关的lncRNA，通过最小绝对收缩和选择算子（LASSO）以及单因素/多因素Cox分析建立与铜死亡相关的lncRNA预测模型。随后，应用时间依赖性受试者工作特征（ROC）和Kaplan-Meier分析评估其预测能力，并通过列线图、单因素/多因素Cox分析和校准曲线对模型进行验证。此外，进行主成分分析（PCA）、免疫分析和基因集富集分析（GSEA），并计算风险组中的50%抑制浓度（IC50）预测值。此外，通过定量实时PCR（qRT-PCR）检测6种与铜死亡相关的lncRNA在HNSCC组织和癌旁组织中的表达。
共筛选出467个lncRNA作为HNSCC组织中与铜死亡相关的lncRNA，建立了一个由AC024075.3、AC090587.2、AC116914.2、AL450384.2、CDKN2A-DT、FAM27E3、JPX和LNC01089组成的8个与铜死亡相关的lncRNA预后特征。对于高危组，结果显示其具有良好的预测性能，总生存期（OS）明显更差。多因素Cox回归证实风险评分是一个可靠的预测因素（95%CI：1.089-1.208，风险比=1.147），1年、3年和5年OS的ROC曲线下面积分别为0.690、0.78524和0.665。差异分析显示，通过qRT-PCR检测，JPX在HNSCC组织中显著上调，而AC024075.3、AC090587.2、AC116914.2、AL450384.2、CDKN2A-DT在HNSCC组织中下调。此外，该基因特征还与一些免疫相关途径和免疫细胞浸润相关，并影响抗癌免疫反应。此外，贝沙罗汀、博来霉素、吉西他滨等被确定为HNSCC的潜在治疗化合物。
这种新的与铜死亡相关的lncRNA预后特征可以预测预后，并有助于为HNSCC提出新的个体化治疗靶点。
