Preoperative plasma anti-DNAJB8 autoantibody and postoperative outcomes in breast cancer: an exploratory analysis.

PURPOSE: We evaluated the clinical significance of plasma autoantibodies against cancer stem cell-associated antigens in breast cancer, with diagnostic performance as the primary endpoint and clinicopathological and prognostic relevance as secondary endpoints. METHODS: In this single-center observational study, autoantibodies against SOX2, survivin, and DNAJB8 were measured using ELISA. The diagnostic performance of anti-DNAJB8 autoantibodies was evaluated in 292 patients with breast cancer and 24 benign controls. Clinicopathological and postoperative analyses were exploratory in a preoperative cohort (175 patients). RESULTS: Only DNAJB8 showed a distinct high-titer subset in the breast cancer group. The primary endpoint was not met, as plasma anti-DNAJB8 autoantibodies showed a non-significant diagnostic performance (AUC, 0.602; 95% CI, 0.488-0.715; P = 0.080). In the preoperative cohort, with six deaths and 11 recurrences, anti-DNAJB8 autoantibody positivity was associated with a worse overall and recurrence-free survival in age-adjusted analyses using Firth's penalized likelihood Cox regression (overall survival: hazard ratio, 10.607; 95% CI, 2.280-61.840; P = 0.003; recurrence-free survival: hazard ratio, 4.329; 95% CI, 1.247-13.082; P = 0.023). CONCLUSION: The primary diagnostic endpoint was not achieved for plasma anti-DNAJB8 autoantibodies. However, anti-DNAJB8 autoantibody positivity was associated with poorer postoperative outcomes, suggesting a hypothesis-generating prognostic relevance.