BRD4-associated chromatin remodelling signature links epigenetic regulation to immune landscape in ovarian cancer

BACKGROUND: Chromatin remodelling-related genes (CRRGs) are essential regulators of gene expression and tumour behaviour. Their role in shaping the immune microenvironment and influencing prognosis in ovarian cancer (OV) remains largely unexplored. We develop a CRRG-based prognostic signature and investigate its association with immune infiltration, particularly plasmacytoid dendritic cells (pDCs). METHODS: We integrated transcriptomic and clinical data from The Cancer Genome Atlas (TCGA; n = 228) and the International Cancer Genome Consortium (ICGC; n = 111) OV cohorts. Differentially expressed CRRGs associated with overall survival were identified and used to construct a prognostic signature via least absolute shrinkage and selection operator and Cox regression. Immune infiltration was analysed using single-sample gene set enrichment analysis (ssGSEA) and validated by multiplex immunofluorescence (mIF). Correlations between CK7+BRD4 expression, pDC infiltration, and chemokine profiles were assessed using public databases and clinical specimens. RESULTS: An 11-gene CRRG-based immune-associated signature was established, effectively stratifying patients into high- and low-risk groups with significantly different overall survival in both cohorts. The risk score was an independent prognostic factor. Immune analyses revealed that high-risk patients exhibited reduced pDC infiltration and lower activation of antigen presentation-related pathways. BRD4 was identified as a key gene negatively correlated with the pDC levels across datasets. High BRD4 expression was associated with poor survival and decreased expression of multiple pDC-attracting chemokines. mIF staining confirmed the inverse correlation between CK7+BRD4 expression and BDCA2+ pDC infiltration in OV tumour tissues. CONCLUSION: Our study proposes a novel CRRG-based prognostic signature linked to the immune features in OV and highlights BRD4 as a potential regulator of pDC infiltration through the suppression of chemokine expression. These findings provide insights into the interplay between epigenetic regulation and the immune landscape in OV, although the implications for immunotherapy responsiveness warrant further investigation.