Comprehensive genomic characterization of early-stage bladder cancer.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.

Sex Disparity in Non-muscle-invasive Bladder Cancer: Pitfalls of Large Population-based Data Sets and Lessons from an Integrated Analysis.

The impact of sex on non-muscle-invasive bladder cancer (NMIBC) remains uncertain and current evidence is conflicting. To address this uncertainty, we conducted an integrative analysis using Surveillance, Epidemiology and End Results (SEER)-Medicare and UROMOL data sets to explore sex disparities in NMIBC oncological outcomes. In the SEER-Medicare cohort, females had lower risks of recurrence and progression in comparison to males, but no significant difference in BC-specific mortality was observed.

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC.