Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Oncology, LiuZhou Traditional Chinese Medical Hospital Affiliated to Guangxi University of Chinese Medicine, Liuzhou, China.
Genet Test Mol Biomarkers. 2024 Mar;28(3):100-113. doi: 10.1089/gtmb.2023.0193. Epub 2024 Mar 13.
Ferroptosis is associated with tumor development; however, its contribution to radioresistant head and neck cancer (HNC) remains unclear. In this study, we used bioinformatics analysis and testing to explore ferroptosis-related genes associated with HNCs radiosensitivity. GSE9714, GSE90761, and The Cancer Genome Atlas (TCGA) datasets were searched to identify ferroptosis-related differentially expressed genes between radioresistant and radiosensitive HNCs or radiation-treated and nonradiation-treated HNCs. A protein-protein interaction analysis on identified hub genes was then performed. Receiver operating characteristic curves and Kaplan-Meier survival analysis were used to assess the diagnostic and prognostic potential of the hub genes. Cell counting kit-8, transwell assay, and flow cytometry were applied to examine the role of hub gene collagen type IV, alpha1 chain () on the proliferation, migration, invasion, and apoptosis of TU686 cells. Hub genes , and showed diagnostic potential for HNC and were negatively correlated with overall survival and disease-free survival in the TCGA dataset. Also, and mRNA levels were significantly increased in TCGA patients with advanced clinical stages or receiving radiotherapy, whereas , and expressions were negatively correlated with immune infiltration. Furthermore, the knockdown of inhibited cell proliferation, migration, and invasion while promoting apoptosis in TU686 cells. Ferroptosis-related hub genes, such as are potential diagnostic and prognostic indicators as well as therapeutic targets for HNC.
铁死亡与肿瘤的发生发展有关；然而，其在头颈部癌症（HNC）放射抵抗中的作用尚不清楚。在本研究中，我们使用生物信息学分析和实验检测来探索与 HNC 放射敏感性相关的铁死亡相关基因。搜索 GSE9714、GSE90761 和癌症基因组图谱（TCGA）数据集，以鉴定放射抵抗和放射敏感 HNC 或放射治疗和非放射治疗 HNC 之间的铁死亡相关差异表达基因。然后对鉴定出的枢纽基因进行蛋白质-蛋白质相互作用分析。受试者工作特征曲线和 Kaplan-Meier 生存分析用于评估枢纽基因的诊断和预后潜力。细胞计数试剂盒-8、Transwell 检测和流式细胞术用于检测枢纽基因胶原 IV 亚型，α1 链（）对 TU686 细胞增殖、迁移、侵袭和凋亡的作用。枢纽基因、和在 HNC 中具有诊断潜力，并且与 TCGA 数据集中的总生存期和无病生存期呈负相关。此外，在 TCGA 患者中，临床分期较晚或接受放疗的患者中，和的 mRNA 水平显著升高，而和的表达与免疫浸润呈负相关。此外，下调抑制 TU686 细胞的增殖、迁移和侵袭，同时促进细胞凋亡。铁死亡相关的枢纽基因，如，可能是 HNC 的潜在诊断和预后指标，也是治疗靶点。
