Association of Histone H3 Trimethylation in Circulating Monocytes with Lack of Early Recurrence in Patients with Bladder Cancer following BCG Induction Therapy

BACKGROUND: The mode of action Bacillus Calmette-Guérin (BCG) in the treatment patients with non-muscle invasive bladder cancer (NMIBC) is incompletely understood, but recent studies support an association between BCG-induced trained immunity circulating monocytes and disease-free survival. OBJECTIVE: We compared epigenetic profiles from NMIBC early disease recurrence those recurrence-free patients. METHODS: conducted chromatin immunoprecipitation DNA sequencing (ChIP-seq) on seven treated BCG (four recurrences three after one year) to determine genome-wide distribution abundance histone 3 lysine 4 trimethylation (H3K4me3) prior five weeks induction therapy. RESULTS: Genome-wide H3K4me3 before or distinguished remaining recurrence-free. Furthermore, levels at genes involved specific pathways were increased group. Independent quantification showed elements Wnt AMPK signaling group initiation, while MAPK same Validation these independent cohort four additional that remained year revealed consistent increases associated pathway CONCLUSIONS: Recurrence-free survival following immunotherapy for accumulation gene loci could lead identification prognostic biomarkers.