The role of cancer-associated fibroblasts secreted POSTN in immune cell infiltration and tumor cell progression in pancreatic cancer

Pancreatic cancer is a highly aggressive malignancy with poor prognosis. Periostin (POSTN) has been associated with advanced disease, yet its functional role within the tumor microenvironment (TME) remains unclear. This study investigated the impact of POSTN on immune infiltration and tumor progression. Public databases including GEPIA2, GEO, TCIA, and Kaplan–Meier Plotter were analyzed to evaluate POSTN expression, prognosis, and immune cell infiltration. Spatial transcriptomics was applied to identify POSTN-related spatial patterns and cell–cell interactions. Functional assays were performed using primary fibroblasts derived from POSTN knock-out and wild-type mice co-cultured with pancreatic cancer cells. High POSTN expression correlated with poor prognosis and increased M2 macrophage infiltration. Spatial analysis revealed POSTN+ fibroblasts surrounding tumor cells. Co-culture with POSTN wild-type fibroblasts significantly enhanced cancer cell migration, invasion, epithelial–mesenchymal transition, and NF-κB signaling. These findings indicate that stromal POSTN promotes tumor progression by remodeling the extracellular matrix and shaping an immunosuppressive microenvironment in pancreatic cancer