Abstract
We have previously reported that the higher expression of TF in human esophageal cancer tissues was significantly associated with tumor invasion, intratumoral microvessel density and patients’ postoperative prognoses. Besides its trans-membranous form, TF also has alternatively spliced transcripts. In the present study, the transcripts of the two TF isoforms, flTF and asTF, in human gastric cancer tissues were determined by real-time PCR, and the correlation between the expression of TF isoforms and patient's clinicopathological features was also analyzed. Our results showed that the relative mRNA expression levels of flTF and asTF in human gastric cancer tissues was significantly higher than those in normal tissues (P=0.035 and P=0.006, respectively). The relative mRNA expression level of asTF was significantly associated with age (P=0.018), meanwhile, we could not find that flTF or asTF expression level was correlated with any other characteristics of the patients, including gender, TNM stage, pathological grade, tumor size, histological type, or chemotherapy sensitivity. Univariate analysis demonstrated that the overall survival rate of gastric cancer patients with lower flTF or asTF expression level was greater than those with higher expression level (P=0.018 and =0.038, respectively). Multivariate COX model analysis also demonstrated that flTF expression (P=0.048) or asTF expression (P=0.002) could be used as independent prognostic predictors in human gastric cancer. Thus, both flTF and asTF mRNA expression levels in cancer tissues could be used as useful risk factors for evaluating the prognoses of patients suffering from gastric cancer.
Highlights
Gastric cancer is an important cancer type occurring in the upper digestive tract, and presents with high morbidity and mortality in China [1]
We have previously reported that the higher expression of Tissue factor (TF) in human esophageal cancer tissues was significantly associated with tumor invasion, intratumoral microvessel density and patients’ postoperative prognoses
Our results showed that the relative mRNA expression levels of full-length TF (flTF) and alternatively-spliced human TF (asTF) in human gastric cancer tissues was significantly higher than those in normal tissues (P=0.035 and P=0.006, respectively)
Summary
Gastric cancer is an important cancer type occurring in the upper digestive tract, and presents with high morbidity and mortality in China [1]. It is important to investigate the molecular mechanisms involved in the transformation and progression of gastric cancer. Tissue factor (TF), a 47-kDa trans-membrane glycoprotein, is a cellular receptor for coagulation factor VII (FVII), activating a clotting cascade involved in many physio-pathological processes [3, 4]. TF could influence protease-activated receptor-dependent tumor cell behavior and regulate integrin function, leading to the intratumoral angiogenesis both in vitro and in vivo [6]. Our previous study demonstrated that the higher expression of TF in human esophageal cancer tissues significantly associated with tumor invasion and intratumoral angiogenesis, suggesting a positive role of TF in cancer progression [3]. Aberrant TF expression could be induced by a majority of oncogenic events, such as activation of K-Ras or epidermal growth factor receptor (EGFR), inactivation of p53 tumor suppressor, and loss of phosphatase and tensin homolog (PTEN) [7,8,9]
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