A Risk Prognostic Model for Patients with Esophageal Squamous Cell Carcinoma Basing on Cuproptosis and Ferroptosis

Background: Cuproptosis, a form of copper-dependent programmed cell death recently presented by Tsvetkov et al., have been identified as a potential therapeutic target for refractory cancers and ferroptosis, a well-known form describing iron-dependent cell death. However, whether the crossing of cuproptosis-related genes and ferroptosis-related genes can introduce some new idea, thus being used as a novel clinical and therapeutic predictor in esophageal squamous cell carcinoma (ESCC) remains unknown.

Methods: We collected ESCC patient data from the Gene Expression Omnibus and the Cancer Genome Atlas databases and used Gene Set Variation Analysis to score each sample based on cuproptosis and ferroptosis. We then performed weighted gene co-expression network analysis to identify cuproptosis and ferroptosis-related genes (CFRGs) and construct a ferroptosis and cuproptosis-related risk prognostic model, which we validated using a test group. We also investigated the relationship between the risk score and other molecular features, such as signaling pathways, immune infiltration, and mutation status.

Results: Four CFRGs (MIDN, C15orf65, COMTD1 and RAP2B) were identified to construct our risk prognostic model. Patients were classified into low- and high-risk groups based on our risk prognostic model and the low-risk group showed significantly higher survival possibilities (P < 0.001). We used the "GO", "cibersort" and "ESTIMATE" methods to the above-mentioned genes to estimate the relationship among the risk score, correlated pathways, immune infiltration, and tumor purity.

Conclusion: We constructed a prognostic model using four CFRGs and demonstrated its potential clinical and therapeutic guidance value for ESCC patients.