EMX2 gene expression predicts liver metastasis and survival in colorectal cancer

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.

EMX2 is epigenetically silenced and suppresses epithelial‑mesenchymal transition in human esophageal adenocarcinoma

“…The results of the present study demonstrated that EMX2 induced the upregulation of E-cadherin and inhibited AKT signaling in OE19 and OE33 cells. Furthermore, the downregulation of EMX2 in lung cancer and colorectal cancer has been associated with decreased overall survival (22,24,28). Therefore, it can be suggested that the downregulation of EMX2 may be associated with a worse EAC prognosis.…”

“…EMX2 serves important roles in cortical development (16), neurogenesis (17,18), early hair cell development (19), the stereociliary bundle orientation of sensory hair cells (20) and mammalian reproduction (21). Recent studies have indicated the potential involvement of EMX2 in various different human cancer types, including lung (22)(23)(24)(25), gastric (26), endometrial (27) and colorectal cancer (28,29). It has also been revealed that EMX2 inhibits the proliferation of lung (23), gastric (26) and colorectal (29) cancer cells, and suppresses the invasive phenotype of lung (23) and colorectal (28,29) cancer cells.…”

The expression of EMX2 lead to cell cycle arrest in glioblastoma cell line

“…Our results are in agreement with reported descriptions of EMX2 as a protein implicated in the progression of some cancers. Indeed, EMX2 has a documented anti-proliferative effect in vitro and anti-tumorigenesis effect in vivo in some solid cancers [ 28 , 45 – 47 ]. In GB cell culture, Falcone et al reported that proliferation inhibition induced by EMX2 was associated with cell collapse and apoptosis activity within 7–8 days [ 31 ].…”

Molecular and Immunohistochemical Markers with Prognostic and Predictive Significance in Liver Metastases from Colorectal Carcinoma

“…Empty Spiracles Homeobox 2 ( EMX2 ) gene has been associated with neuronal growth and differentiation [ 57 ]. qtRT-PCR technology and siRNA-mediated knockdown and adenoviral delivery-mediated overexpression of EMX2 were performed showing that colorectal tumor samples had decreased EMX2 expression levels, and its downregulation was associated with distant metastasis concluding that overexpression of EMX2 led to an inhibition of tumor cell migration [ 57 ].…”