A Novel Ferroptosis-Related Biomarker Signature to Predict Overall Survival of Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) accounts for the main esophageal cancer (ESCA) type, which is also associated with the greatest malignant grade and low survival rates worldwide. Ferroptosis is recently discovered as a kind of programmed cell death, which is indicated in various reports to be involved in the regulation of tumor biological behaviors. This work focused on the comprehensive evaluation of the association between ferroptosis-related gene (FRG) expression profiles and prognosis in ESCC patients based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). ALOX12, ALOX12B, ANGPTL7, DRD4, MAPK9, SLC38A1, and ZNF419 were selected to develop a novel ferroptosis-related gene signature for GEO and TCGA cohorts. The prognostic risk model exactly classified patients who had diverse survival outcomes. In addition, this study identified the ferroptosis-related signature as a factor to independently predict the risk of ESCC. Thereafter, we also constructed the prognosis nomogram by incorporating clinical factors and risk score, and the calibration plots illustrated good prognostic performance. Moreover, the association of the risk score with immune checkpoints was observed. Collectively, the proposed ferroptosis-related gene signature in our study is effective and has a potential clinical application to predict the prognosis of ESCC.

Automated summary

This study focused on evaluating the association between ferroptosis-related gene expression profiles and prognosis in ESCC patients, developing a new ferroptosis-related gene signature that accurately classified patients with diverse survival outcomes in GEO and TCGA cohorts. The signature was identified as an independent predictor of ESCC risk and showed potential clinical application for predicting prognosis.