Unmasking the Hypoxia Landscape in Cervical Cancer: S100A2 and Its Implication for Immunotherapy Resistance

Cervical cancer is the fourth most common cancer in women worldwide and typically diagnosed between the ages of 35 and 44. Despite the death rate declining 1% each year since the 2000s, the 5-year survival of late stage remains lower than 20%. This emphasizes the urgency to keep exploring cervical cancer cell survival factors and identifying new prognostic markers. In this issue of Reproductive Sciences, Yang et al. stratified hypoxia subtype by analyzing 200 hypoxia-related genes in TCGA database and observed patient overall survival, hypoxic, transcriptome, genomics, and immunological characteristics vary among these hypoxia subtypes and created a hypoxia score which successfully stratified patient by predicting clinical outcomes and response to immunotherapy. Simultaneously, a hypoxia mediator (S100A2) associated with an aggressive cervical cancer phenotype is identified. We reviewed similar work on S100A2 and hypoxia-mediated multidrug resistance and highlighted the values added by this study. Future work could focus on unraveling the direct link between S100A2 and immunotherapy resistance.