Distinct Epigenetic Signatures Underpin the Molecular Classification of Low- and High-Grade NMIBC

ABSTRACT: Non-muscle invasive bladder cancer (NMIBC) is marked by a high rate of recurrence and clinical heterogeneity, yet its epigenetic underpinnings remain poorly defined. Here, we present a comprehensive, genome-scale analysis of the NMIBC epigenetic landscape, integrating reduced representation bisulfite sequencing (RRBS), transcriptomic profiling, chromatin state analysis, and immunohistochemistry on patient-derived healthy urothelium and tumor samples. We identified thousands of differentially expressed genes (DEGs) and hundreds of differentially methylated regions (DMRs) distinguishing tumor from normal tissue, with expression–methylation correlations highlighting key pathways implicated in NMIBC pathogenesis. Stratification by tumor grade revealed distinct epigenetic alterations and immune-related signatures associated with progression, including non-coding RNAs (ncRNAs) exhibiting stepwise methylation and expression changes from healthy tissue to low- and high-grade tumors. These findings were validated using publicly available data from The Cancer Genome Atlas (TCGA). Our study defines robust grade-specific epigenetic signatures in NMIBC, offering new insights into tumor biology and presenting potential biomarkers for improved grading, prognostication, and personalized patient management.

ORGANISM(S): Homo sapiens

PROVIDER: GSE304874 | GEO | 2026/07/01

REPOSITORIES: GEO