Abstract
BackgroundMDM4 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.ResultsThe 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 MethodsWe 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.ConclusionsMDM4 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.
Highlights
Gastric cancer, a common malignant tumor, remains a major cause of death worldwide despite its decreased incidence over past decades [1, 2]
The qRT-PCR and the Western blot analysis showed that the MDM4 expression level was high in GTACN+ but not in GTACN−
The influence of overall prognosis relies on whether or not the high MDM4 expression level could lead to lymph node metastasis (LNM)
Summary
A common malignant tumor, remains a major cause of death worldwide despite its decreased incidence over past decades [1, 2]. About 90% to 95% of Gastric cancers are adenocarcinomas. Lymph node metastasis (LNM) is an important prognostic factor in gastric cancer [3, 4]. Among patients with R0 resection for gastric cancer, LN status is the most important independent prognostic factor, followed by pT category, surgical complication, and distant metastasis [5]. No accurate and reliable judgment of preoperative LNM has been established for patients with GTAC. Enhanced computed tomography (CT) is routinely used to evaluate LNM in gastric cancer, with a sensitivity of 80.0% and a specificity of 77.8% based on the size of LN [6]. 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
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