BICC1 and neoplasm: JAK2-STAT3 signaling is critical to cell proliferation, angiogenesis, invasion, and immune evasion of tumors.38 The CXCL1 expression was reported to depend on the JAK2-STAT3 signaling.39 CXCL1 is secreted by various cell types in tumor microenvironments, such as CAFs, and immune cells.40 We found that the treatment with recombinant LCN2 protein also induced the expression of CXCL1 in CAFs and THP-1 cells (Supplementary Fig. 26), suggesting that stroma cells are probably also involved in BICC1-induced angiogenesis of PAAD.