Correlation of TNFAIP8 overexpression with the proliferation, metastasis, and disease-free survival in endometrial cancer

Abstract

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is an apoptosis regulator proven to have an important function in the proliferation, invasion, metastasis, and progression of malignancies. In this study, we investigated the clinical role of TNFAIP8 overexpression in endometrial cancer (EC) and determined the relationship of TNFAIP8 with the proliferative antigen Ki-67 and metastasis-related gene matrix metallopeptidase 9 (MMP9) in 225 tumor specimens by immunohistochemistry and western blot, in order to elucidate more information on the role of TNFAIP8 protein with regard to the pathogenesis of EC. An association was observed between TNFAIP8 overexpression and clinicopathologic factors, such as advanced International Federation of Gynecology and Obstetrics stage (P<0.001), higher histologic grade (P=0.017), deep myometrial invasion (P=0.030), lymphovascular space invasion (P=0.011), lymph node metastasis (P<0.001), and recurrence. Furthermore, TNFAIP8 overexpression was strongly correlated with MMP9 and Ki-67 expression in the progression of ECs. Patients with high expression of TNFAIP8 (P<0.001 for both) and Ki-67 (P=0.007 and P=0.008) had poor overall survival and disease-free survival (DFS) rates. MMP9 overexpression did not affect survival outcomes (P>0.05). Multivariate Cox regression analysis revealed that TNFAIP8 (P=0.029) and lymph node metastasis (P=0.022) were independent factors of DFS in patients with EC. These findings suggested that TNFAIP8 may be used as a prognostic marker for the recurrence of EC, and its promotion of the proliferation and metastasis in EC may be due to its mediation of Ki-67 and MMP9.