TNFAIP8 Overexpression: Clinical Relevance to Esophageal Squamous Cell Carcinoma

Abstract

Tumor necrosis factor alpha-induced protein 8 (TNFAIP8) is a suppressor of TNF-α mediated apoptosis, and its expression is induced by NF-κB activation. TNFAIP8 expression is significantly increased in various cancer cell lines. A correlation between TNFAIP8 overexpression, cancer progression, and poor prognosis has been described in many reports of human solid cancers. To clarify the functional and clinical significance of the cancer progression-related gene, TNFAIP8, in esophageal squamous cell carcinoma (ESCC), we used immunohistochemistry to demonstrate TNFAIP8 expression in ESCC. Next, TNFAIP8 expression was depleted by using siRNA to examine the function of TNFAIP8 in the proliferation and apoptosis induction of ESCC cell lines. We detected correlations between TNFAIP8 expression and TNM stage (P < 0.001), tumor depth (P = 0.002), lymph node metastasis (P = 0.013), distant metastasis (P = 0.001), lymphatic invasion (P < 0.001), and venous invasion (P < 0.001) among the clinicopathological characteristics of ESCC patients, and high TNFAIP8 expression was found in poor survival. TNFAIP8 depletion was significantly associated with apoptosis induction after cisplatin administration and reduced proliferation. Our results suggest that TNFAIP8 might be an effective therapeutic target for ESCC in the future.