Abstract
BackgroundThe Empty Spiracles Homeobox (EMX-) 2 gene has been associated with regulation of growth and differentiation in neuronal development. While recent studies provide evidence that EMX2 regulates tumorigenesis of various solid tumors, its role in colorectal cancer remains unknown. We aimed to assess the prognostic significance of EMX2 expression in stage III colorectal adenocarcinoma.MethodsExpression levels of EMX2 in human colorectal cancer and adjacent mucosa were assessed by qRT-PCR technology, and results were correlated with clinical and survival data. siRNA-mediated knockdown and adenoviral delivery-mediated overexpression of EMX2 were performed in order to investigate its effects on the migration of colorectal cancer cells in vitro.ResultsCompared to corresponding healthy mucosa, colorectal tumor samples had decreased EMX2 expression levels. Furthermore, EMX2 down-regulation in colorectal cancer tissue was associated with distant metastasis (M1) and impaired overall patient survival. In vitro knockdown of EMX2 resulted in increased tumor cell migration. Conversely, overexpression of EMX2 led to an inhibition of tumor cell migration.ConclusionsEMX2 is frequently down-regulated in human colorectal cancer, and down-regulation of EMX2 is a prognostic marker for disease-free and overall survival. EMX2 might thus represent a promising therapeutic target in colorectal cancer.
Highlights
The Empty Spiracles Homeobox (EMX-) 2 gene has been associated with regulation of growth and differentiation in neuronal development
Patient cohort A total of 31 patients with International Union Against Cancer (UICC) stage III adenocarcinoma of the colon or rectum were included in the study
Down-regulation of Empty Spiracles Homeobox 2 (EMX2) was significantly associated with higher T and N-stage as well as metachronous liver metastases
Summary
The Empty Spiracles Homeobox (EMX-) 2 gene has been associated with regulation of growth and differentiation in neuronal development. While recent studies provide evidence that EMX2 regulates tumorigenesis of various solid tumors, its role in colorectal cancer remains unknown. While screening programs have led to a reduction in colorectal cancer mortality, there is considerable room for improvement in identifying prognostic markers that predict which patients are at risk for metastatic disease [2, 3]. Aberrant signaling of homeobox genes has been shown in many types of cancer [13]. EMX2 has been shown to be a predictive marker for survival in lung cancer [18]. To our knowledge, no study has evaluated the role of EMX2 in colorectal cancer far.
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