BRD4-Associated Chromatin Remodeling Signature Links Epigenetic Regulation to Immune Landscape in Ovarian Cancer

Background Chromatin remodeling-related genes (CRRGs) are essential regulators of gene expression and tumor behavior. Their role in shaping the immune microenvironment and influencing prognosis in ovarian cancer (OV) remains largely unexplored. This study aimed to 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 TCGA (n = 228) and ICGC (n = 111) ovarian cancer cohorts. Differentially expressed CRRGs associated with overall survival were identified and used to construct a prognostic signature via LASSO and Cox regression. Immune infiltration was analyzed using ssGSEA and validated by multiplex immunofluorescence (mIF). Correlations between 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 the TCGA and ICGC 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 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 BRD4 expression and BDCA2 ⁺ pDC infiltration in OV tumor tissues. Conclusion This study proposes a novel CRRG-based prognostic signature linked to immune features in OV and highlights BRD4 as a potential regulator of pDC infiltration through 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.