Abstract

MDS1 and EVI1 complex locus protein EVI1 (<i>MECOM</i>) is an oncogenic transcription factor in many types of cancer. However, the clinical significance of <i>MECOM</i> in esophagogastric cancer has not been well elucidated. The aim of this study was to define the association of amplification of MECOM and esophagogastric cancer patients’ overall survival rate and to investigate the functional role of <i>MECOM</i> in MKN45 cell proliferation and apoptosis. In this study, a total of 3236 esophagus and gastric patients were analyzed from 16 genomic studies using cBioPortal, which provides an open-access resource with multiple cancer genomics data sets. When the patient samples were divided into two subgroups (<i>MECOM</i> amplified group and <i>MECOM</i> non-amplified group), the poor survival rate was significantly associated with <i>MECOM</i> amplification (<i>p</i>= 0.04). To investigate the role of EVI1 on esophagogastric cancer cells, siRNA dependent gene silencing of EVI1 in MKN45 cells was conducted. RT-PCR was used to examine the expression of EVI1 in MKN45 cells. The MTT assay was used to examine cell proliferation. The apoptotic cells were quantified by fluorescence cell counter. Knockdown of EVI1 leads to reduced cell proliferation and induced apoptosis in MKN45 cells. These results indicate that <i>MECOM</i> may be a potential target for esophagus and gastric cancer gene-targeted therapy. Collectively, our result suggested that EVI1 is a probable target gene for esophagogastric cancer cell proliferation.

Highlights

  • The esophagus and stomach are the parts of the upper gastrointestinal (GI) tract and both show similar features [1]

  • The purpose of this study is to determine the functional role of MECOM, especially EVI1, on esophagogastric cancer cells which may affect esophagogastric cancer patients’ survival rate

  • The previous study identified that the MECOM amplification had been observed at myeloid malignancies and that MECOM amplification associated with MECOM mRNA overexpression [18]

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Summary

Introduction

The esophagus and stomach are the parts of the upper gastrointestinal (GI) tract and both show similar features [1]. Esophagogastric cancer shows exceptionally high rates of death limited to Asia. Gastric cancer in the early stage is typically small and shows less symptoms than other cancers which can delay the diagnosis. The mortality rate of gastric cancer increases rapidly, leading it to be the second deadliest cancer worldwide [2]. Esophageal cancer displays a dangerous presentation which includes unresectable carcinoma or metastases, which is visible through radiographic technology [3]. The detection and prevention of the cancer is very complicated since it shows two histologic types: squamous cell carcinoma (SCC) and adenocarcinoma (ACE) [4]

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