The integrated analysis of PRDX3 in lung cancer: biomarker potential and therapeutic target prospects.

Abstract

Background: Lung cancer remains the malignant tumor with the highest global incidence and mortality, posing a severe threat to public health. Peroxiredoxin 3 (PRDX3), a well-characterized ferroptosis biomarker, has been implicated in lung cancer progression. Accumulating evidence suggests that PRDX3 may serve as a core gene and potential biomarker, which is critical for elucidating pathogenesis, improving diagnostic accuracy, and developing targeted therapeutic strategies for lung cancer.

Methods: To systematically investigate the expression pattern of PRDX3 and its clinical relevance in lung cancer, we integrated multiple bioinformatics tools and public datasets to analyze PRDX3 expression across pan-cancer cohorts, major lung cancer subtypes, and patient subgroups stratified by sex, age, and clinical stage. Furthermore, we evaluated the correlation between PRDX3 expression and immunotherapeutic-related factors, and performed multivariate survival analysis to validate its independent prognostic value. Additionally, protein-protein interaction (PPI) networking and co-expression analysis were employed to explore the functional interactions of PRDX3 with core ferroptosis regulators and immune microenvironment modulators.

Results: PRDX3 was significantly upregulated in multiple malignant tumors, including LUAD and LUSC, with minimal variations in expression levels across different sex, age, and clinical stage subgroups. High PRDX3 expression was independently associated with significantly poorer clinical prognosis in lung cancer, particularly in the LUAD subtype. Pathway enrichment analysis revealed that immune activation, immune inhibition, and MHC molecule-related signaling pathways were closely correlated with altered PRDX3 expression in both LUAD and LUSC, with distinct subtype-specific patterns. PPI networking demonstrated that PRDX3 exhibited positive co-expression with core ferroptosis regulators (GPX4, TXN2) and interacted with components of the thioredoxin system (TXNRD2, TXN), indicating its potential involvement in regulating cellular redox homeostasis and ferroptosis. Single-cell analysis further confirmed PRDX3 expression in lung cancer cells and key immune cell subsets (T cells, macrophages), with higher expression levels observed in LUAD than in LUSC.

Conclusions: These correlative findings suggest that PRDX3 may play a pivotal role in lung cancer pathogenesis, potentially through mechanisms involving ferroptosis regulation via interaction with GPX4 and the thioredoxin system, redox homeostasis maintenance, and subtype-specific immune microenvironment modulation. Collectively, PRDX3 represents a promising independent prognostic biomarker for lung cancer, especially for LUAD, and a potential therapeutic target for ferroptosis-based and immunotherapeutic strategies.