AUTHOR=Yang Lina , Hai Jingyu , Liu Jiayi , Shen Shaohua , Su Lin , Sun Juan 

TITLE=Prognostic significance and therapeutic implications of redox metabolism-related genes in head and neck squamous cell carcinoma

JOURNAL=Experimental Biology and Medicine

VOLUME=Volume 250 - 2025

YEAR=2025

URL=https://www.ebm-journal.org/journals/experimental-biology-and-medicine/articles/10.3389/ebm.2025.10623

DOI=10.3389/ebm.2025.10623

ISSN=1535-3699

ABSTRACT=Head and neck squamous cell carcinomas (HNSC) are associated with alterations in redox metabolism. This study aims to identify differentially expressed genes (DEGs) related to redox metabolism in HNSC and assess their prognostic values. We utilized the limma package for identifying redox metabolism-related DEGs and performed univariate and multivariate Cox regression analyses to evaluate their prognostic significance. Gene set variation analysis (GSVA), immune cell infiltration analysis, and single-cell RNA sequencing were utilized to explore the relationships between gene expression and tumor processes. Chemotherapy sensitivity was assessed based on ERP44 expression levels. Additionally, pan-cancer analysis was conducted to evaluate ERP44 expression and its prognostic value across different cancer types. The analysis identified several DEGs with significant prognostic value, including ERP44, which was significantly associated with poor prognosis in HNSC patients. High ERP44 expression correlated with reduced overall survival, disease-specific survival, and progression-free interval. ERP44 was notably overexpressed in tumor tissues and associated with key oncogenic pathways and immune cell infiltration patterns. Chemotherapeutic drug sensitivity analysis revealed that high ERP44 expression increased sensitivity to Paclitaxel, Vinblastine, and Sorafenib but decreased sensitivity to Rapamycin. Pan-cancer analysis indicated that ERP44 is differentially expressed and prognostic across multiple cancer types. Our findings highlight the crucial role of redox metabolism-related DEGs, particularly ERP44, in HNSC progression and prognosis. ERP44 serves as a potential biomarker for prognosis and therapeutic response, warranting further research into its biological functions and potential as a therapeutic target.