Pan-cancer analysis reveals BAF complexes as immune-related biomarkers and validation in triple-negative breast cancer.

AIMSBAF complexes (BAFs), ATP-dependent regulators of chromatin structure, play a significant role in cancer progression. This pan-cancer study aimed to decode the potential of specific BAFs in the pathology, immunity, and therapy of targeted cancers.

MATERIALS AND METHODSData were retrieved from The Cancer Genome Atlas, Gene Expression Omnibus, and IMvigor210 databases and were analyzed for expression patterns, prognostic value, mutational signatures, biological pathways, tumor immune microenvironment (TIME) remodeling, and therapeutic resistance of BAFs. Experimental validation was also conducted.

KEY FINDINGSBAFs exhibit abnormal expression in various human cancers. The BAFs model and nomogram (based on multiple variables) were developed as prognostic tools. BAFs regulate the TIME and influence the response to anti-PD-L1 therapy, particularly through ACTL6A, as observed in RNA sequencing and single-cell RNA sequencing datasets (high-resolution gene expression data at the single-cell level). ACTLA6 is a major adverse gene in the prognostic model. Patients with high ACTL6A expression showed significantly worse overall survival (hazard ratio = 1.32, 95 % CI: 1.26-1.39, p < 0.001). ACTL6A expression escalates with breast cancer (BRCA) malignancy, particularly in triple-negative BRCA (TNBC), and correlates with immune checkpoint expression while playing a crucial role in promoting cancer metastasis in TNBC.

SIGNIFICANCEOur findings first emphasize the significance of a novel BAFs model for patient prognosis and corroborate the considerable role of BAFs as immune-related biomarkers in pan-cancer progression. ACTL6A has a dual role as an immune-related biomarker and potential therapeutic target in TNBC, deepening our comprehension of its function as an oncogene.