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Peer-reviewedCC BY 4.0Frontiers in Oncology

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

  • HuaRong Luo1,2
  • ChengDang Xu1,2
  • YiFan Liu1,2
  • YiWen Yao2,3
  • ZuJun Sun2,3
  • Yan Gu2,4
  • TianRu Wang1,2
4 affiliations
  1. 1Department of Urology, Tongji Hospital of Tongji University
  2. 2School of Medicine, Tongji University
  3. 3Department of Laboratory Medicine, Tongji Hospital of Tongji University
  4. 4Department of Gastrointestinal Surgery, Tongji Hospital of Tongji University
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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.

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Cite

BibTeXRIS
BibTeX
@article{luo2026association,
  title = {{Association of MAGEA4 expression with molecular and immune subtypes and clinical outcomes in recurrent bladder cancer}},
  author = {HuaRong Luo and ChengDang Xu and YiFan Liu and YiWen Yao and ZuJun Sun and Yan Gu and TianRu Wang},
  journal = {Frontiers in Oncology},
  year = {2026},
  month = oct,
  doi = {10.3389/fonc.2026.1906141},
  url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1906141/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Association of MAGEA4 expression with molecular and immune subtypes and clinical outcomes in recurrent bladder cancer
AU  - HuaRong Luo
AU  - ChengDang Xu
AU  - YiFan Liu
AU  - YiWen Yao
AU  - ZuJun Sun
AU  - Yan Gu
AU  - TianRu Wang
PY  - 2026
DA  - 2026/10/15
JO  - Frontiers in Oncology
DO  - 10.3389/fonc.2026.1906141
UR  - https://www.frontiersin.org/articles/10.3389/fonc.2026.1906141/full
AB  - 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.
SN  - 2234-943X
ER  -