Predictive and prognostic value of ACSL4 and GPX4 in patients with esophageal squamous cell carcinoma receiving post-operative radiotherapy

Abstract Objective: Although multimodality treatment, including chemoradiotherapy and surgery has significantly improved the prognosis of patients with esophageal squamous cell carcinoma (ESCC), a valid predictor is crucial for individualized treatment. As acyl-CoA synthetase long-chain family member 4 (ACLS4) and glutathione peroxidase 4 (GPX4) are key genes with radiation responses and constituents of the ferroptosis signaling pathway, the present study adopted ACSL4 and GPX4 protein expression to explore their predictive and prognostic value in patients with ESCC receiving adjuvant radiotherapy. Methods: A total of 108 patients with thoracic ESCC who had undergone radical surgery and adjuvant radiotherapy were enrolled in the present retrospectively study. ACSL4 and GPX4 immunohistochemistry experiments were performed on paraffin-embedded tumor samples. The prognostic value of ACSL4 and GPX4 was examined using survival analysis, and the predictive value of ACSL4 and GPX4 for long-term survival was examined using univariate and multivariate Cox regression analyses, and verified by receiver operating characteristic (ROC) analysis. Results: The survival analysis revealed that overall survival (OS) and disease-free survival (DFS) were significantly longer in the high ACSL4 expression group, and the DFS was significantly shorter in the high GPX4 expression group. The results of univariate and multivariate Cox regression analyses revealed that the ACSL4 expression level was an independent predictor for OS and DFS, and that the GPX4 expression level was an independent predictor for DFS. ROC analysis verified the predictive role of ACSL4 expression for DFS and OS, with an area under the curve of 0.713 and 0.663. Conclusion: The present study demonstrates that ACSL4 and GPX4 may serve as valuable prognostic biomarkers for long-term survival, and play a key translational role in individualized therapy for patients with ESCC.