Construction of a Ferroptosis-Related Gene Signature for Head and Neck Squamous Cell Carcinoma Prognosis Prediction

Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers, and few studies have demonstrated the value of ferroptosis-related genes in prognosis.

Methods

The original counts of RNA sequencing data and clinicopathological data were obtained from TCGA and GSE65858 datasets. Common ferroptosis-related genes related to prognosis were identified from the training set and were included in LASSO to determine the best prognosis. To evaluate the efficacy, time-dependent ROC and Kaplan–Meier (KM) survival analyses were applied. Moreover, univariate and multivariate Cox regression analyses were used to screen independent parameters of prognosis and build a nomogram. Eventually, possible biological pathways were proposed based on GSEA.

Results

Among 242 ferroptosis-related genes, we identified that the FLT3, IL6, Keap1, NQO1, SOCS1 and TRIB3 genes were significantly connected with HNSCC patient prognosis as a six-gene signature. After, the patients were divided into high- and low-risk groups based on the six-gene signature. The KM survival curves demonstrated that the high-risk group had worse OS (p < 0.0001) and higher AUC values (0.654, 0.735, and 0.679 for 1-, 3-, and 5-year survival, respectively) for the prognostic signature of the six genes compared with other genes, which were also validated in the GSE65858 dataset. Moreover, GSEA suggested that the epithelial mesenchymal transition pathway was abundant and that the mesenchymal status in the high-risk group was substantially higher than that in the low-risk group. Finally, the immune microenvironment and differences in the content of immune cell types were demonstrated.

Conclusion

We established a six-ferroptosis-related-gene model crossing clinical prognostic parameters that can predict HNSCC patient prognosis and provide a reliable prognostic evaluation tool to assist clinical treatment decisions.

Keywords:

• head and neck squamous cell carcinoma
• ferroptosis
• prognosis
• TCGA

Abbreviations

HNSCC, Head and Neck Squamous Cell Carcinoma; TCGA, The Cancer Genome Atlas; LASSO, the Least Absolute Shrinkage and Selection Operator; GSEA, Gene Set Enrichment Analysis; GEO, Gene Expression Omnibus; KM, Kaplan–Meier; ROC, Receiver Operating Characteristic; HPV, Human Papilloma Virus.

Data Sharing Statement

The data are available from the corresponding author upon reasonable request.

Ethical Committee Approval and Informed Consent

The study was performed based on the TCGA and GEO public databases. Because no personal identifying information was used in the current study, it was granted an exemption from ethics approval from the Institutional Review Board of the Ningbo Medical Center Lihuili Hospital.

Acknowledgment

This work was supported by the Zhejiang Provincial Natural Science Foundation of China [LY19H160014; LQ21H130001], Ningbo Medical and Health Brand Discipline [No. PPXK2018-02], Medical and Health Research Project of Zhejiang Province [2019ZD018; 2021KY307], Ningbo Natural Science Foundation [202003N4239], and Ningbo “Technology Innovation 2025” Major Special Project [2020Z098; 2018B10015].

Disclosure

The authors declare no conflicts of interest.