Title: First large-scale prospective evaluation of serum S100A6 as a complementary biomarker for early pancreatic cancer detection. In a large cohort study, the authors demonstrated, for the first time, the diagnostic potential of serum S100A6 in PC. When combined with CA19-9, serum S100A6 improves diagnostic performance for both overall and early-stage pancreatic cancer. This is a new, important clinical marker.