Work

Association of MAGEA4 expression with molecular and immune subtypes and clinical outcomes in recurrent bladder cancer

Year: 2026

Type: article

Abstract: Background: This study assessed MAGEA4 expression in recurrent bladder cancer, examined its relationships with molecular and immune subtypes, and evaluated its association with treatment response and prognosis. Methods: This single-center exploratory cohort study enrolled 20 patients. RNA sequencing was performed on recurrent tumor tissue samples. The EU molecular subtypes were determined. Immune subtypes were classified, and PD-L1 and HER2 status were assessed. GO, KEGG, and Reactome enrichment analyses were performed. Patients were divided into MAGEA4-high and MAGEA4-low groups using the cohort median expression level. Differences in the composition of molecular/immune subtypes were compared. Within-cohort ROC analysis was used to assess discrimination of clinical benefit, and PFS was analyzed using Kaplan-Meier and Cox methods. Results: The top 20 genes with the most prominent between-subtype expression differences were identified. Genes upregulated in the Luminal papillary subtype were enriched in terms related to cell-cell junctions and epithelial structure maintenance. Downregulated genes were enriched in pathways associated with immune activation and inflammatory infiltration. Enrichment signals involved the PI3K-Akt, MAPK, neuroactive ligand-receptor interaction, and JAK-STAT pathways. Significant differences in PD-L1 status, TMIT subtypes, and EU subtypes were observed between MAGEA4-high and MAGEA4-low groups, and the six MAGEA4-immune/molecular association tests remained below q<0.05 after Benjamini-Hochberg correction. MAGEA4 expression also differed according to PD-L1 status, TMIT subtype, and binary EU subtype grouping. Within-cohort ROC analysis yielded AUC values of 0.798, 0.800, and 0.750 in the overall, immunotherapy, and combination-therapy cohorts, respectively; the bootstrap optimism-corrected overall AUC was 0.793. High MAGEA4 expression was associated with shorter PFS. Conclusion: MAGEA4 expression was associated with PD-L1 status, TMIT immune subtypes, and EU molecular subtypes, showed within-cohort discrimination of clinical benefit, and was associated with poorer PFS. These findings support further evaluation of MAGEA4 as a candidate molecular stratification marker in independent cohorts.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1906141