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

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.

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).

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.

CCDC69 delineates an immune-active, favorable-risk BRCA state with potential prognostic and therapy-related value, warranting experimental and clinical validation.