Integrative multi-omics analysis identifies CCDC69 as a marker associated with germinal center B-cell infiltration in TNBC: development and validation

Although coiled-coil domain containing 69 (CCDC69) has been implicated in tumor biology, its role in triple-negative breast cancer (TNBC) and immune regulation remains unclear. Bulk transcriptomic data, single-cell RNA sequencing datasets, and spatial transcriptomics were used to investigate the role of CCDC69 in TNBC. Germinal center B-cell (GCB) signatures were quantified using single-sample gene set enrichment analysis (ssGSEA), and their associations with CCDC69 expression were assessed using correlation, ROC, and logistic regression analyses. An independent external TNBC cohort (GSE58812) was used to validate the association between CCDC69 expression, GCB infiltration, and survival outcomes. CCDC69 expression was significantly downregulated in breast cancer tissues but was associated with favorable survival outcomes in TNBC patients. CCDC69 expression positively correlated with multiple immune cell populations, particularly B cells and plasma cells. Single-cell RNA sequencing demonstrated that CCDC69 expression was enriched in B-lineage cells, especially GCB. Spatial transcriptomic analyses further showed that CCDC69-high regions were spatially co-localized with B-cell-rich and germinal center-like immune niches. In the TCGA TNBC cohort, CCDC69 expression was strongly associated with GCB infiltration and effectively distinguished GCB-high tumors. Logistic regression analysis confirmed that CCDC69 was independently associated with GCB enrichment. Findings were validated in the GSE58812 cohort. CCDC69 expression correlated with GCB-related signatures, showed good discriminative performance in identifying GCB-high tumors, and was associated with improved patient outcomes when combined with GCB enrichment. CCDC69 is closely associated with B-cell-mediated immune responses and germinal center niches in TNBC. Our findings suggest that CCDC69 may serve as a robust biomarker of immune activation and favorable prognosis.