The overexpression of MDM4: an effective and novel predictor of gastric adenocarcinoma lymph node metastasis

Abstract

Background: MDM4 is the important negative regulator of the tumor suppressor protein p53, which is overexpressed in various human cancers. This study evaluates the MDM4 expression in patients with gastric adenocarcinoma (GTAC) at the mRNA and protein levels and examines relationships among MDM4 expression, clinicopathological features, and prognosis.

Results: The qRT-PCR and the Western blot analysis showed that the MDM4 expression level was high in GTACN⁺ but not in GTACN⁻. The high expression level of MDM4 was significantly associated with age (P = 0.047), lymph node metastasis (LNM) (P < 0.001), pathological stage (P < 0.001), differentiation status (P = 0.001), and preoperative serum CA19-9 level (P < 0.001). Moreover, the survival analysis showed that Borrmann type, depth of invasion, LNM, and preoperative serum CA19-9 level were independent prognostic factors. The univariate analysis revealed that MDM4 expression influenced GTAC prognosis. Furthermore, the influence of overall prognosis relies on whether or not the high MDM4 expression level could lead to LNM.

Materials and Methods: We investigated MDM4 expression in primary GTAC and paired normal gastric tissues (30 pairs) through qRT-PCR and Western blot analyses. We also performed immunohistochemistry analysis on 336 paraffin-embedded GTAC specimens and 33 matched normal specimens.

Conclusions: MDM4 expression may result in LMN of GTAC. High MDM4 expression levels are associated with LMN of GTAC and influence the prognosis of patients with GTAC.