UBE2S and HIF1α expression patterns and stratified analysis reveal prognostic value in esophageal squamous cell carcinoma

Background The prognostic heterogeneity of esophageal squamous cell carcinoma (ESCC) necessitates robust biomarkers. Although hypoxia-inducible factor 1 α (HIF1 α ) is implicated in ESCC progression, its interplay with ubiquitin-conjugating enzyme E2S (UBE2S) remains uncharacterized. Methods We investigated UBE2S and HIF1 α expression via immunohistochemistry (IHC) in a cohort of 259 ESCC patients. Transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used for validation. Prognostic value was assessed using Kaplan–Meier and multivariate Cox regression analyses. Stratified analysis was employed to identify high-risk subgroups. Results UBE2S and HIF1 α were significantly overexpressed in ESCC tissues at both protein and mRNA levels. UBE2S expression correlated with nationality (Kazak vs. Han, p = 0.001) and vessel invasion ( p = 0.020), while HIF1 α associated with gender ( p = 0.040) and depth of invasion ( p = 0.050). Multivariate analysis identified UBE2S as an independent prognostic factor for overall survival (OS; HR = 1.685, p = 0.041). Notably, co-expression analysis revealed that patients with UBE2S-positive/HIF1 α -positive tumors had the poorest prognosis. Conclusion In conclusion, our multi-platform data suggest that UBE2S and HIF1 α may represent critical biomarkers in ESCC. Their consistent overexpression and association with adverse outcomes support their potential for improving risk stratification and lay the groundwork for exploring them as future therapeutic targets.