Integrative Transcriptomic Profiling Reveals Histone Variant–Driven Immune Escape in Breast Cancer
Abstract:
Immune evasion is a central and critical challenge in oncotherapy, often driven by complex transcriptional remod elling. This study presents a systems-level in-silico analysis of breast cancer transcriptomes to uncover a novel im mune escape mechanism mimicking autoimmune stress. Using differential expression analysis (logFC > 2.0, FDR < 0.001), we discovered coordinated upregulation of histone variants (e.g., H2AC19, H3C11, H2AX, H4C8, H2BC21) with immune-related genes (MHC class II, complement, Fc receptors), patterning a robust SLE-like gene module (40 genes, FDR = 7.49 × 10⁻³³). Functional enrichment via Gene ontology and KEGG pathways revealed signatures of antigen processing, immune receptor activity, and chromatin remodeling. These findings propose chronic antigenic as important outcome of this mimicry, with complement and Fc receptor upregulation potentially recruiting immunosup pressive cells. Our results position chromatin remodeling, particularly via histone variants, as an upstream regulator of immune dysfunction, offering in-silico derived targets to overcome immunotherapy resistance. This study combines transcriptomic profiling and enrichment analysis to better understand tumor-immune interactions in breast cancer.
