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

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.

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.

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.

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.