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

Jiahang Song,Yanhu Liu,Xiang Guan,Qingguo Li,Xun Zhang,Wenda Yu

doi:10.3389/fmolb.2021.675193

Abstract

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.

Highlights

Esophageal cancer (ESCA), a global malignancy, ranks sixth and eighth in terms of tumor-related mortality and morbidity of all tumors, respectively
least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were performed in the training set to identify seven ferroptosis-related genes (ALOX12, ALOX12B, ANGPTL7, DRD4, MAPK9, SLC38A1, and ZNF419) for constructing a novel prognostic signature (Figure 1)
The results showed that ALOX12, ANGPTL7, DRD4, and MAPK9 remarkably decreased within Esophageal squamous cell carcinoma (ESCC) samples relative to noncarcinoma samples, whereas SLC38A1 and ZNF419 were highly expressed

Summary

Introduction

Esophageal cancer (ESCA), a global malignancy, ranks sixth and eighth in terms of tumor-related mortality and morbidity of all tumors, respectively. ESCA is associated with a dismal prognostic outcome, and its five-year survival rate has been reported to be 15–25%. Esophageal squamous cell carcinoma (ESCC) accounts for a major ESCA subtype, which is predominant in eastern Asia (Matsushima et al, 2010). The poor outcome of ESCC is associated with its insidious initial symptoms, susceptibility to metastasis, resistance to radiotherapy, and tumor recurrence (Pennathur et al, 2013). Over the past few years, multidisciplinary and surgical treatments have been developed, but the median survival of ESCC cases is only 10 months (Wang et al, 2020a). Considering the limited prediction of prognosis for ESCC patients, there is an urgent need for the exploration of novel biomarkers

Methods

Results

Conclusion