Zhang Shuaiyuan, Zhang Lujin, Lu Huanzi, Yao Yihuan, Liu Xiaoyong, Hou Jingsong
Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, China.
Front Oncol. 2022 Aug 22;12:955336. doi: 10.3389/fonc.2022.955336. eCollection 2022.
The purpose of this study was to identify the prognostic value of cuproptosis and copper metabolism-related genes, to clarify their molecular and immunological characteristics, and to elucidate their benefits in head and neck squamous cell carcinoma (HNSCC).
The details of human cuproptosis and copper metabolism-related genes were searched and filtered from the msigdb database and the latest literature. To identify prognostic genes associated with cuproptosis and copper metabolism, we used least absolute shrinkage and selection operator regression, and this coefficient was used to set up a prognostic risk score model. HNSCC samples were divided into two groups according to the median risk. Afterwards, the function and immune characteristics of these genes in HNSCC were analyzed.
The 14-gene signature was constructed to classify HNSCC patients into low-risk and high-risk groups according to the risk level. In the The Cancer Genome Atlas (TCGA) cohort, the overall survival (OS) rate of the high-risk group was lower than that of the low-risk group (P < 0.0001). The area under the curve of the time-dependent Receiver Operator Characteristic (ROC) curve assessed the good performance of the genetic signature in predicting OS and showed similar performance in the external validation cohort. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment assays and Protein-Protein Interaction (PPI) protein networks have been used to explore signaling pathways and potential mechanisms that were markedly active in patients with HNSCC. Furthermore, the 14 cuproptosis and copper metabolism-related genes were significantly correlated with the immune microenvironment, suggesting that these genes may be linked with the immune regulation and development of HNSCC.
Our results emphasize the significance of cuproptosis and copper metabolism as a predictive biomarker for HNSCC, and its expression levels seem to be correlated with immune- related features; thus, they may be a possible biomarker for HNSCC prognosis.
本研究旨在确定铜死亡及铜代谢相关基因的预后价值，阐明其分子和免疫特征，并揭示其在头颈部鳞状细胞癌（HNSCC）中的作用。
从msigdb数据库和最新文献中搜索并筛选人类铜死亡及铜代谢相关基因的详细信息。为了鉴定与铜死亡和铜代谢相关的预后基因，我们使用了最小绝对收缩和选择算子回归，并将该系数用于建立预后风险评分模型。根据中位风险将HNSCC样本分为两组。随后，分析了这些基因在HNSCC中的功能和免疫特征。
构建了14基因特征，根据风险水平将HNSCC患者分为低风险和高风险组。在癌症基因组图谱（TCGA）队列中，高风险组的总生存率（OS）低于低风险组（P < 0.0001）。时间依赖性受试者工作特征（ROC）曲线下面积评估了基因特征在预测OS方面的良好性能，并且在外部验证队列中表现相似。基因本体论和京都基因与基因组百科全书富集分析以及蛋白质-蛋白质相互作用（PPI）蛋白网络已用于探索在HNSCC患者中明显活跃的信号通路和潜在机制。此外，14个铜死亡和铜代谢相关基因与免疫微环境显著相关，表明这些基因可能与HNSCC的免疫调节和发展有关。
我们的结果强调了铜死亡和铜代谢作为HNSCC预测生物标志物的重要性，其表达水平似乎与免疫相关特征相关；因此，它们可能是HNSCC预后的一个可能生物标志物。
