Pan-cancer prioritization of CCDC69 reveals an immune-enriched and therapeutically sensitive breast cancer phenotype

BACKGROUND: Coiled-coil domain-containing protein 69 (CCDC69) has been implicated in tumor biology, but its pan-cancer immunogenomic context and relevance to breast cancer remain insufficiently defined. METHODS: We integrated The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) transcriptomes, paired tumor-normal comparisons, diagnostic modeling, survival analyses, copy-number and genomic-instability profiling, immune-cycle and immune-infiltration analyses, single-cell and spatial transcriptomic datasets, pathway enrichment, immunotherapy cohorts, pharmacogenomic resources and molecular docking to characterize CCDC69 across cancers and in breast invasive carcinoma (BRCA). RESULTS: CCDC69 was broadly dysregulated across cancers and showed cancer-type-dependent diagnostic value. Pan-cancer survival analyses revealed context-specific prognostic effects, with BRCA showing consistent favorable associations for disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI). Further analyses linked CCDC69 to copy-number states, stemness, genomic instability and multiple immune phenotypes. Integrated prioritization highlighted BRCA as a representative tumor context. In BRCA, higher CCDC69 expression was associated with less advanced clinicopathological features, immune-enriched microenvironments, increased cancer-immunity-cycle activity, diverse immune-cell infiltration and compartment-specific expression across tumor, immune and stromal regions. Pathway analyses connected CCDC69 with immune activation, interferon response and lymphocyte-related programs, while showing inverse associations with proliferation, DNA repair and cell-cycle signatures. Immunotherapy and drug-sensitivity analyses suggested context-dependent response-stratification and therapeutic relevance. CONCLUSION: CCDC69 delineates an immune-active, favorable-risk BRCA state with potential prognostic and therapy-related value, warranting experimental and clinical validation.