Ferroptosis-Associated Genes GSTZ1 and MT1G Orchestrate Multidimensional Remodeling of the Nasopharyngeal Carcinoma Microenvironment via the TGF-β Signaling

Background: Nasopharyngeal carcinoma (NPC) progression involves dynamic interactions between ferroptosis and tumor microenvironment (TME) remodeling, yet the regulatory roles of ferroptosis-related genes (GSTZ1, PTGS2, MT1G) remain poorly characterized. This study aimed to dissect their multidimensional networks and therapeutic implications in NPC. Methods: Through bioinformatics analysis and machine learning algorithms (including XGBoost-driven prognostic modeling), we systematically investigated the expression patterns, pathway interactions, and immune modulation of these hub genes. KEGG enrichment, immune infiltration deconvolution, and survival analyses were performed in NPC. Results: The ferroptosis-associated genes exhibited NPC-specific dysregulation: GSTZ1 and MT1G are lowly expressed in NPC, while PTGS2 is highly expressed.The prognostic model integrating these genes achieved superior predictive accuracy (AUC >0.9). In addition A novel TGF-β‒tryptophan metabolic axis was identified, coordinating epithelial-mesenchymal transition (EMT) and immunosuppression.Immunologically, GSTZ1 showed dual regulation—positively correlating with B cells/CD4+ TRM cells but suppressing M1 macrophages, whereas PTGS2 promoted M1 polarization while inhibiting follicular helper T cells. Interestingly, Pulsatilla chinensis can target regulated Ferroptosis-Associated genens to inhibit tumor progression. Conclusion: This research found that Ferroptose-related genes GSTZ1、PTGS2、MT1G as multifunctional regulators bridging ferroptosis, metabolic reprogramming, and immune evasion in NPC.we also found thatthese demonstrated co-promote NPC TME.The TGFβ signaling pathway, as a connecting bridge, provides a deeper understanding of the important molecular mechanisms by which ferroptosis induces the progression of NPC