Biglycan Secreted by Tumor Stromal Cells Is a Predictive Marker for the Early Recurrence of Pancreatic Cancer

Pancreatic cancer carries a poor prognosis due to its dense fibrotic stroma and high rate of metastatic recurrence. Reliable biomarkers for early detection and recurrence prediction remain lacking. We previously reported that biglycan (BGN), derived from tumor endothelial cells, a key component of the cancer stroma, promotes tumor progression by enhancing angiogenesis, cell migration, and metastasis. This study aimed to evaluate the association between BGN expression in pancreatic cancer and early recurrence. We performed immunohistochemistry for BGN and collagen fibers on resected pancreatic cancer tissues from 98 patients who underwent curative resection. Quantitative analyses included BGN-positive area, tumor fibrosis area, and cross-linked collagen area. In addition, a BGN-knockout (BGN-KO) mouse pancreatic tumor model was generated to investigate the functional role of BGN in the tumor microenvironment. It revealed that both the BGN-positive area and cross-linked collagen area were significantly increased in the early recurrence group compared with the 5-year survival group. In the mouse model, BGN-KO tumors exhibited significantly reduced fibrosis and cross-linked collagen deposition, features indicative of decreased tumor stiffness, compared with tumors in wild-type (WT) mice. Thus, BGN contributes to tumor stromal stiffness and may serve as a predictive biomarker for early recurrence in pancreatic cancer.