Tissue Factor as a Prognostic and Therapeutic Biomarker in Resected Pancreatic Cancer

Tissue factor (TF), a key initiator of the coagulation cascade, is frequently overexpressed in pancreatic cancer and linked to tumor progression and thrombosis. While TF has been recognized as a prognostic biomarker, its clinical relevance in surgically treated patients remains unclear.

We retrospectively analyzed TF expression in resected pancreatic cancer specimens from 265 patients, including those with and without preoperative therapy, using immunohistochemistry. Tissue factor expression was semiquantitatively classified as negative, low, or high. Associations with clinicopathological features, treatment response, and survival were evaluated.

High TF expression was observed in 17.4% of cases and was significantly associated with elevated CA19-9, biologically borderline resectable disease, and lymph node metastases. These patients had shorter overall survival (median overall survival: 20.6 vs. 38.8 vs. 53.6 months, p < 0.001). High TF expression remained an independent predictor of poor prognosis (hazard ratio [HR]: 2.21, p = 0.0002). Tissue factor-negative tumors were associated with favorable outcomes, including long-term survival despite recurrence. Tissue factor expression decreased following preoperative therapy but did not correlate with histological response.

Tissue factor expression stratifies pancreatic cancer into biologically and prognostically distinct subgroups. While high TF expression indicates aggressive disease and poor survival, TF-negative tumors represent an indolent, treatment-sensitive subtype. These findings underscore the biological heterogeneity of pancreatic cancer and support TF as a clinically relevant prognostic biomarker.