Prognostic Significance of Tissue Factor in Pancreatic Ductal Adenocarcinoma

Abstract

Tissue factor (TF) is a transmembrane glycoprotein that plays roles in the blood coagulation and intracellular signaling pathways, and has also been suggested to modulate the biological behavior of cancer cells. In order to examine the clinicopathologic significance of TF expression in pancreatic ductal adenocarcinoma, TF expression was determined by immunohistochemistry using a newly raised anti-TF monoclonal antibody in 113 patients who had undergone surgical resection of pancreatic ductal adenocarcinoma. According to the incidence of tumor cell immunopositivity, patients were divided into ''negative TF'' (0%), ''weak TF'' (<25%), or ''high TF'' (25% or more) groups, which accounted for 11.6% (n = 13), 44.2% (n = 50), and 44.2% (n = 50) of the total, respectively. Increased TF expression was correlated with the extent of the primary tumor (P = 0.0043), lymph node metastasis (P = 0.0043), lymphatic distant metastasis (P = 0.0039), advanced tumor-node-metastasis stage (P = 0.0002), and high tumor grade (P = 0.0164). Multivariate analysis using the Cox proportional hazards model showed that high TF expression was an independent negative predictor for survival (hazard ratio, 2.014; P = 0.0076). Moreover, patients with TF-negative tumors had a significantly better prognosis even if lymph node metastasis was present (P < 0.0001). We also showed that TF knockdown by RNA interference suppressed the invasiveness of a pancreatic adenocarcinoma cell line in vitro. These results indicate that TF expression may contribute to the aggressiveness of pancreatic ductal adenocarcinoma by stimulating tumor invasiveness, and that evaluation of the primary tumor for TF expression may identify patients with a poor prognosis.

Tissue factor expression correlates with disease‐specific survival in patients with node‐negative muscle‐invasive bladder cancer

“…[9][10][11]16 While the precise mechanism by which TF is responsible for poor outcomes in cancer patients is still under investigation, several in vivo experiments have demonstrated its contribution to hematogenous tumor angiogenesis and metastasis. 3,19,20,22,23 Zhang et al showed that in vivo sarcoma cells overexpressing TF grew more rapidly and established larger and more vascularized tumors than cells underexpressing TF.…”

“…10 Recently, similar results were published for pancreatic, ovarian and hepatocellular carcinoma. [11][12][13] Moreover, patients with TF negative pancreatic tumors had a significantly better prognosis even if lymph node disease was present.…”

Human alternatively spliced tissue factor is not secreted and does not trigger coagulation

“…Although recombinant asTF shortened the clotting time of platelet poor plasma [1], asTF was enriched in human thrombi [1] and triggered activation of factor (F)X when secreted by human umbilical vein endothelial cells (HUVEC) [4], asTF expressed by human embryonic kidney (HEK) cells failed to activate FX [5]. To further explore the putative role of asTF in coagulation, we studied the procoagulant properties of asTF cloned from HUVEC in an expression model of MIA PaCa-2 cells, a human pancreatic TF-deficient cell line [2,[6][7][8]. Using these cells, confounding factors such as concurrent expression of TF are excluded.…”

Effect of Tissue Factor on Invasion Inhibition and Apoptosis Inducing Effect of Oxaliplatin in Human Gastric Cancer Cell

“…Recent research shows that TF involved in cell signal transduction, supplying important protection to embryonic development and maintaining body functions, has certain effects on tumor angiogenesis, tumor growth, and metastasis (Toomey et al, 1997). TF expression level increases in certain types of malignant tumors, including gastric cancer, colon cancer, and pancreatic cancer (Nakasaki et al, 2002;Nitori et al, 2005;Yamashita et al, 2007). Level increase was closely related to MVD, malignant tumor staging, and prognosis (Jiao et al, 2005).…”