Overexpression of TNFAIP8 is associated with tumor aggressiveness and poor prognosis in patients with invasive ductal breast carcinoma

Abstract

Tumor necrosis factor α-induced protein 8 (TNFAIP8), a transcription factor nuclear factor κB-inducible, antiapoptotic and oncogenic molecule, is associated with prognosis of several human malignancies. However, the relationship between TNFAIP8 and the prognosis of the invasive ductal carcinoma (IDC) of the breast remains unclear. TNFAIP8 expression was evaluated using real-time polymerase chain reaction (PCR) and Western blot analysis in 20 fresh IDC tissues and immunohistochemical analysis in 351 paraffin-embedded IDC tissues. Real-time PCR and Western blot analysis demonstrated that both TNFAIP8 messenger RNA and protein were up-regulated in IDC tissues compared with the paired adjacent noncancerous tissues. Immunohistochemistry revealed that TNFAIP8 expression was significantly correlated with some clinicopathological factors, including axillary lymph node metastasis (P=.001), advanced TNM stage (P<.001), high histologic grade (P<.001), molecular subtype (P<.001), and postoperative recurrence (P<.001). Univariate and multivariate logistic regression analyses demonstrated that TNFAIP8 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 1.818; 95% confidence interval, 1.167-2.832; P=.008). Moreover, Kaplan-Meier analysis indicated that IDC patients with high TNFAIP8 expression had a shorter survival time than did those with low TNFAIP8 expression, and multivariate analysis indicated that TNFAIP8 was an independent prognostic factor for overall survival and disease-free survival in IDC (P=.041 and P=.020, respectively). Therefore, TNFAIP8 overexpression may contribute to tumor progression, and it may be a novel prognostic biomarker for the patients with IDC.

Keywords: Axillary lymph node metastasis; Breast cancer; Invasive ductal carcinoma (IDC); Prognosis; Tumor necrosis factor α–induced protein 8 (TNFAIP8).