Abstract
The clinical TNM staging system is currently used to evaluate the prognosis of head and neck squamous cell carcinoma (HNSCC). The 5-year survival rate for patients with HNSCC is less than 50%, which is attributed to the lack of reliable prognostic biomarkers. Ferroptosis-related genes (FRGs) regulate cancer initiation and progression. Therefore, we analyzed the correlation between FRGs and the clinical outcomes of patients with HNSCC. A typical prognostic model of FRGs for HNSCC was constructed using bioinformatics tools and data from public databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and GeneCards. The model was generated based on the following six FRGs: ATG5, PRDX6, OTUB1, FTH1, SOCS1, and MAP3K5. The accuracy of model prediction was analyzed systematically. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. The AUC for 1-year, 3-year, and 5-year survival were 0.645, 0.721, and 0.737, respectively, in the training set (TCGA cohort) and 0.726, 0.620, and 0.584, respectively, in the validation set (GSE65858). The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that six FRGs were enriched in the ferroptosis pathway. A novel FRG prognostic signature model was established for HNSCC. The findings of this study reveal that FRGs are potential biomarkers for HNSCC.
Highlights
Head and neck carcinoma (HNC), which is one of the top 10 tumors, accounts for 3% of all cancer cases
A prognostic model was constructed for six Ferroptosis-related genes (FRGs) based on the expression levels of eight FRGs and the multivariate Cox regression analysis
The best prognostic gene signature was selected based on the lowest Akaike information criterion (AIC) value (Table 2)
Summary
Head and neck carcinoma (HNC), which is one of the top 10 tumors, accounts for 3% of all cancer cases. The genetic, biochemical, and morphological characteristics of ferroptosis are classified under the category of iron-dependent cell death and accumulation of superoxide lipids [8]. Few studies have been conducted on iron-induced death in head and neck cancers, and even fewer studies have suggested that ferroptosis is associated with HNSCC pathogenesis [14, 15]. The prognostic value of FRG in HNSCC must be evaluated. Correlations between the expression profiles of FRGs and clinical outcomes in patients with HNSCC were analyzed using clinical datasets curated in public databases. The Cox regression analysis was performed to analyze the prognostic value of six FRGs in HNSCC. The correlation between these six FRGs and the TME of HNSCC was examined. The findings of this study reveal that FRGs are potential biomarkers for HNSCC
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