Prognostic Impact of Nectin4 and IRF6 Expression in Patients Undergoing Radical Cystectomy for Muscle-Invasive Bladder Cancer.
- 1Department of Urology, University Hospital of Zürich, Zürich, Switzerland.
- 2Institute of Pathology and Molecular Pathology, University Hospital of Zürich, Zürich, Switzerland.
- 3Department of Urology, Stadtspital Triemli, Zürich, Switzerland.
Abstract
Background/aim
Reliable biomarkers to stratify prognosis in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) remain limited. This study investigated whether the expression of the recently emerging proteins Nectin4 and interferon regulatory factor 6 (IRF6) is associated with pathological stage and oncological survival outcomes in patients undergoing RC for MIBC.Materials and methods
Two tissue microarrays comprising of 163 patients treated with RC for MIBC were analyzed at the University Hospital of Zürich. Immunohistochemistry was performed for Nectin4 and IRF6, staining intensity was quantified using H-scores. Associations with pathological stage were assessed using logistic regression. Progression-free survival (PFS) and cancer-specific survival (CSS) were evaluated using Cox regression and Kaplan-Meier analysis.Results
Higher Nectin4 and cytoplasmic IRF6 expression were significantly associated with lower pathological T-stage and AJCC stage (p<0.01). Patients with Nectin4 positive tumors had longer PFS compared to Nectin4 negative cases [hazard ration (HR)=0.50, 95% confidence interval (CI)=0.28-0.90; p=0.020]. Similarly, higher IRF6 expression was linked to longer PFS (HR=0.71, 95%-CI=0.52-0.96, p=0.028). No strong significant association between Nectin4 or IRF6 and CSS was observed. Both markers were not able to independently predict PFS or CSS after adjustment for American Joint Committee on Cancer stages in multivariable analysis.Conclusion
Stronger Nectin4 and IRF6 expression is associated with less aggressive histopathological characteristics in patients undergoing RC for bladder cancer. Higher Nectin4 and IRF6 expression were further linked to a longer PFS in univariable analysis, but not independent of other prognostic factors.
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BibTeX
@article{enderlin2026prognostic,
title = {{Prognostic Impact of Nectin4 and IRF6 Expression in Patients Undergoing Radical Cystectomy for Muscle-Invasive Bladder Cancer.}},
author = {Dominik Enderlin and Maria Gloor and Uwe Bieri and Alekhya Mazumdar and Souzan Salemi and Niels Rupp and Holger Moch and Daniel Eberli and Cédric Poyet},
journal = {Cancer diagnosis \& prognosis},
year = {2026},
month = nov,
doi = {10.21873/cdp.10597},
url = {https://europepmc.org/article/MED/42968952},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Prognostic Impact of Nectin4 and IRF6 Expression in Patients Undergoing Radical Cystectomy for Muscle-Invasive Bladder Cancer.
AU - Dominik Enderlin
AU - Maria Gloor
AU - Uwe Bieri
AU - Alekhya Mazumdar
AU - Souzan Salemi
AU - Niels Rupp
AU - Holger Moch
AU - Daniel Eberli
AU - Cédric Poyet
PY - 2026
DA - 2026/11/01
JO - Cancer diagnosis & prognosis
DO - 10.21873/cdp.10597
UR - https://europepmc.org/article/MED/42968952
AB - Background/aim Reliable biomarkers to stratify prognosis in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) remain limited. This study investigated whether the expression of the recently emerging proteins Nectin4 and interferon regulatory factor 6 (IRF6) is associated with pathological stage and oncological survival outcomes in patients undergoing RC for MIBC.Materials and methods Two tissue microarrays comprising of 163 patients treated with RC for MIBC were analyzed at the University Hospital of Zürich. Immunohistochemistry was performed for Nectin4 and IRF6, staining intensity was quantified using H-scores. Associations with pathological stage were assessed using logistic regression. Progression-free survival (PFS) and cancer-specific survival (CSS) were evaluated using Cox regression and Kaplan-Meier analysis.Results Higher Nectin4 and cytoplasmic IRF6 expression were significantly associated with lower pathological T-stage and AJCC stage (p<0.01). Patients with Nectin4 positive tumors had longer PFS compared to Nectin4 negative cases [hazard ration (HR)=0.50, 95% confidence interval (CI)=0.28-0.90; p=0.020]. Similarly, higher IRF6 expression was linked to longer PFS (HR=0.71, 95%-CI=0.52-0.96, p=0.028). No strong significant association between Nectin4 or IRF6 and CSS was observed. Both markers were not able to independently predict PFS or CSS after adjustment for American Joint Committee on Cancer stages in multivariable analysis.Conclusion Stronger Nectin4 and IRF6 expression is associated with less aggressive histopathological characteristics in patients undergoing RC for bladder cancer. Higher Nectin4 and IRF6 expression were further linked to a longer PFS in univariable analysis, but not independent of other prognostic factors.
SN - 2732-7787
ER -