Tumor necrosis factor α-induced protein 8 expression as a predictor of prognosis and resistance in patients with advanced ovarian cancer treated with neoadjuvant chemotherapy

Abstract

We explored the correlation of tumor necrosis factor α-induced protein 8 (TNFAIP8) with platinum resistance in ovarian cancers treated with neoadjuvant chemotherapy (NACT). We observed a significant trend of decreased TNFAIP8 expression after NACT (P = .042), and the extent of decreased TNFAIP8 expression after NACT was positively associated with response to NACT (P = .013). Interestingly, in patients treated with NACT, the extent of decreased TNFAIP8 expression after NACT in tumor (change in immunohistochemistry scores ≤-1 versus ≥0; P = .001) correlated significantly with overall survival. Furthermore, TNFAIP8 knockout inhibited tumor proliferation in a time-dependent manner and arrested the cell cycle in the G0/G1 phase in OVCAR-3 cells. In vitro, OVCAR-3 cells with down-regulated TNFAIP8 exhibited greater chemosensitivity as well as increased autophagy-related protein (Beclin 1 and LC II) expression. We propose that the degree of decreased TNFAIP8 expression is a biomarker for predicting NACT resistance, and TNFAIP8 may be involved in cisplatin-induced chemoresistance by interacting with autophagy-related proteins and may be a therapeutic target for ovarian cancer treatment.

Keywords: Neoadjuvant chemotherapy; Ovarian cancer; Platinum resistance; Survival; TNFAIP8.