Ferroptosis-Related Genes Are Associated with Radioresistance and Immune Suppression in Head and Neck Cancer.

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.