Ji Zao, Fang Zhiyao, Dong Xue, Wang Jia, Wan Xianyao, Yan Aihui
Department of Otolaryngology, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Department of Critical Care Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, 116021, China.
Eur Arch Otorhinolaryngol. 2022 Nov;279(11):5277-5288. doi: 10.1007/s00405-022-07433-4. Epub 2022 Jul 12.
Laryngeal cancer (LC) is a common malignant tumor of the head and neck. However, the relationship between ferroptosis and LC is still unclear. The aim of this study was to identify potential ferroptosis-related biomarkers for diagnosis and prognosis in LC.
We screened differentially expressed genes (DEGs) related to ferroptosis in LC from the TCGA and FerrDb database. DEGs were identified and enrichment by GO/KEGG, GSEA, GSVA analysis. PPI analysis was performed using String and Cytoscape, then hub genes were extracted. Furthermore, ROC analysis, pan-cancer analysis, gene mutation analysis, immune infiltration correlation analysis and clinical correlation analysis of hub genes were performed.
A total of 59 DEGs were screened, which were more significantly enriched in biological processes and involved in HIF-1 signaling pathway, serotonergic synapse and ferroptosis. A total of 29 significant gene set pathways of LC data were performed by GSEA analysis. The GSVA analysis obtained 53 significant differential gene set pathways. The top 20 genes were identified by PPI. ROC curves revealed four of the top20 genes had a good performance, which were CA9 (AUC = 0.930), MAPK3 (AUC = 0.915), MUC1 (AUC = 0.945), and NOX4 (AUC = 0.933). Subsequent analysis found that CDKN2A has the highest mutation frequency in the top 20 gene, and IFNG had a significant correlation with age, tumor stage, degree of tumor differentiation and lymphatic clearance surgery.
Our study identified key genes closely related to ferroptosis in LC, which still need more studies to explore the mechanisms involved and may become effective clinical diagnostic and prognostic biomarkers.
喉癌（LC）是头颈部常见的恶性肿瘤。然而，铁死亡与喉癌之间的关系仍不清楚。本研究的目的是确定喉癌诊断和预后中潜在的铁死亡相关生物标志物。
我们从TCGA和FerrDb数据库中筛选了与喉癌铁死亡相关的差异表达基因（DEG）。通过GO/KEGG、GSEA、GSVA分析对DEG进行鉴定和富集。使用String和Cytoscape进行蛋白质-蛋白质相互作用（PPI）分析，然后提取枢纽基因。此外，还对枢纽基因进行了ROC分析、泛癌分析、基因突变分析、免疫浸润相关性分析和临床相关性分析。
共筛选出59个DEG，这些基因在生物学过程中富集更显著，参与缺氧诱导因子-1（HIF-1）信号通路、血清素能突触和铁死亡。通过基因集富集分析（GSEA）对喉癌数据的29个显著基因集通路进行了分析。GSVA分析获得了53个显著的差异基因集通路。通过PPI鉴定出前20个基因。ROC曲线显示，前20个基因中有4个表现良好，分别是碳酸酐酶9（CA9，曲线下面积[AUC]=0.930）、丝裂原活化蛋白激酶3（MAPK3，AUC=0.915）、粘蛋白1（MUC1，AUC=0.945）和烟酰胺腺嘌呤二核苷酸磷酸氧化酶4（NOX4，AUC=0.933）。后续分析发现，细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）在这前20个基因中的突变频率最高，而干扰素γ（IFNG）与年龄、肿瘤分期、肿瘤分化程度和淋巴清扫手术显著相关。
我们的研究确定了与喉癌铁死亡密切相关的关键基因，仍需更多研究来探索其中涉及的机制，这些基因可能成为有效的临床诊断和预后生物标志物。
