Nucleoporin 188 as a Predictive Biomarker of Poor Prognosis in Muscle-invasive Bladder Cancer.

Background/aim: Muscle-invasive bladder cancer (MIBC) represents a significant clinical challenge due to its aggressive nature. Identifying reliable biomarkers to predict prognosis is critical for improving patient outcomes. Nucleoporin 188 (NUP188), a component of nuclear pore complexes, has emerged as a potential candidate, yet its role in MIBC remains underexplored.

Materials and methods: This study analyzed NUP188 expression across multicenter MIBC cohorts from TCGA, GSE48075, and GSE169455, as well as the immunotherapy cohorts, using Kaplan-Meier survival analysis and Cox regression to assess prognostic significance. In vitro assays in 5637 and UM-UC-3 cell lines evaluated the effects of NUP188 knockdown on proliferation and migration. Pathway enrichment and Gene Set Variation Analysis (GSVA) were employed to investigate mechanistic associations.

Results: Elevated NUP188 expression was consistently associated with poor overall survival, progression-free interval, and disease-specific survival across MIBC cohorts, establishing it as an independent adverse prognostic factor. In the immunotherapy cohorts, high NUP188 levels correlated with reduced survival and immunotherapy non-responsiveness. In vitro, NUP188 silencing significantly suppressed proliferation and migration of MIBC cell lines. In addition, NUP188 was linked to metabolic reprogramming, particularly lipid metabolism, and exhibited distinct mutational profiles.

Conclusion: NUP188 emerges as a novel biomarker predictive of poor prognosis in MIBC. Its influence on cellular proliferation, migration, and metabolic pathways underscores its potential as a therapeutic target.