Li Yunshan, Sun Caidie, Gu Feihan, Yue Jiayuan, Huang Xu, Yuan Bin, Wang Yuanyin, Chen Ran
College and Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral Diseases Research of Anhui Province, Hefei, China.
Department of Pharmacology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
J Biomol Struct Dyn. 2024 Jan 27:1-12. doi: 10.1080/07391102.2024.2308776.
Patients with head and neck squamous cell carcinoma (HNSCC) have a poor prognosis because of their high recurrence and metastasis rates. Cuproptosis is a novel type of copper-dependent cell death that differs from apoptosis, necroptosis, and cytosolic scorch death. We designed and validated an individualized cuproptosis-related gene (CRG) signature for risk evaluation and prognostic prediction in HNSCC patients. Ninety differentially expressed CRGs were found in HNSCC. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were performed to investigate the functional involvement of CRGs in the Cancer Genome Atlas (TCGA) HNSCC cohort. A CRG signature was created using 10 genes after univariate and multivariate analysis. Kaplan Meier (KM) analysis showed that the survival rate of the high-risk group was significantly lower than that of the low-risk group. Multivariate regression analysis identified risk scores based on prognostic characteristics as independent prognostic indicators of HNSCC. Moreover, risk models are related to tumor mutational burden (TMB), tumor-infiltrating immune cells (TICs), immune checkpoints, clinical characteristics, and antitumor drug susceptibility. Furthermore, we found that CuCl treatment promoted cuproptosis in HNSCC cells, and that the expression levels of cuproptosis-related genes were altered by different doses of CuCl. In summary, understanding the detailed molecular mechanisms of cuproptosis and its impact on overall survival (OS), and identifying potential therapeutic targets for HNSCC will provide potential insights for treatment.
头颈部鳞状细胞癌（HNSCC）患者由于其高复发率和转移率，预后较差。铜死亡是一种新型的铜依赖性细胞死亡，不同于凋亡、坏死性凋亡和细胞质焦亡。我们设计并验证了一种个性化的铜死亡相关基因（CRG）特征，用于HNSCC患者的风险评估和预后预测。在HNSCC中发现了90个差异表达的CRG。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，以研究CRG在癌症基因组图谱（TCGA）HNSCC队列中的功能参与情况。经过单变量和多变量分析后，使用10个基因创建了一个CRG特征。Kaplan Meier（KM）分析表明，高危组的生存率显著低于低危组。多变量回归分析确定基于预后特征的风险评分是HNSCC的独立预后指标。此外，风险模型与肿瘤突变负荷（TMB）、肿瘤浸润免疫细胞（TIC）、免疫检查点、临床特征和抗肿瘤药物敏感性相关。此外，我们发现氯化铜处理可促进HNSCC细胞中的铜死亡，并且不同剂量的氯化铜会改变铜死亡相关基因的表达水平。总之，了解铜死亡的详细分子机制及其对总生存期（OS）的影响，并确定HNSCC的潜在治疗靶点，将为治疗提供潜在的见解。
