Prognostic Significance of Thymosin- 4 in Gastric Adenocarcinoma Patients

ABSTRACT

Background: Thymosin- 4 is an actin-sequestering protein that regulates actin polymerization. It is known to be associated with cell migration, angiogenesis and wound healing, as well as with tumor metastasis. Methods: We immunohistochemically evaluated the thymosin- 4 expression in gastric adenocarcinoma specimens, the relationship between this protein and the pathologic features and other tumor-related proteins, and its influence on the patient outcome. Results: We demonstrated that 40 specimens (26.3%) of 152 gastric adenocarcinomas showed positivity for thymosin- 4. The thymosin- 4 expression was statistically associated with advanced tumor stage (p=0.010), the nodal stage (p=0.029), the TNM stage (p=0.008), and the presence of lymphovascular invasion (p=0.009). The thymosin- 4 protein expression was closely related to the positivity for VEGF (p=0.000), c-Myc (p=0.007), and cyclin D1 (p=0.005), but it was not associated with the E-cadherin (p=0.861) or -catenin (p=0.640) expressions. The median survival and disease relapse time of patients showing thymosin-4 immunoreactivity were statistically shorter than those of patients without expression. Multivariate analysis showed that the tumor stage (p=0.003), nodal stage (p=0.005), thymosin- 4 expression (p=0.019) and Lauren's classification (p=0.037) were statistically important prognostic factors for gastric adenocarcinomas. Conclusions: The thymosin- 4 expression might be associated with disease progression of gastric adenocarcinomas and it should be regarded as an important prognostic factor for estimating patient survival.