MDM4 as a Prognostic Factor for Patients With Gastric Cancer With Low Expression of p53.

Abstract

The oncoproteins murine double minute (MDM) 2 and MDM4 inactivate tumor-suppressor protein p53. Their mutual relationship with the prognosis of gastric cancer (GC) remains unknown. Expression of MDM2, MDM4, and p53 in tumors of 241 patients with GC were evaluated immunohistochemically. Effects of overexpression of MDM4 on tumor-growth properties and sensitivity to cytotoxic drugs were investigated using NUGC4 human GC cell line. High expression of p53 was associated with poor overall survival in the whole population. Among 173 patients with low expression of p53 (implying nonmutation), high expression of MDM4 was an independent factor of poor prognosis in both stage I-III and IV, but of MDM2 was not. MDM4-transduced NUGC4 cells formed twice as many colonies and had a higher 50% inhibitory concentration for 5-fluorouracil and oxaliplatin than did the control cells. MDM4 expression is a factor conferring poor prognosis in patients with GC with low expression of p53 and may confer drug resistance.