Esophageal adenocarcinoma (EAC) is an aggressive and challenging disease to treat, with an overall five-year survival rate of <20%. Early malignant cell dissemination contributes to this poor prognosis. Epithelial-mesenchymal transition (EMT) induces the invasion and metastasis of carcinoma cells. Empty spiracles homeobox 2 (EMX2) is a homeodomain-containing transcription factor, which is associated with numerous cancer types, and has been demonstrated to regulate EMT. In the present study, 48 pairs of EAC and adjacent normal tissues were analyzed. The results revealed that EMX2 was downregulated in EAC tissues, and its expression was negatively correlated with the DNA hypermethylation of its promoter. Additionally, the OE19 and OE33 EAC cell lines were treated with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine, and the results indicated that EMX2 expression was increased. Overexpressing EMX2 in EAC cell lines enhanced the expression of apoptotic markers, inhibited cell migration and invasion, led to the upregulation of E-cadherin and the downregulation of mesenchymal markers, and suppressed AKT, mTOR and S6K phosphorylation. Furthermore, EMX2 overexpression sensitized EAC cells to cisplatin. These results demonstrated that EMX2 inhibited the AKT/mTOR/S6K signaling pathway and decreased EMT. However, the downregulation of EMX2 was revealed to be associated with EMT in EAC, indicating that EMX2 may be a potential target for the management of EAC.
The fatality rate of esophageal carcinomas is high in developing countries, making effective treatment desirable. Traditional treatment has now entered into the platform, and treatments based on the detection of biomarkers increasingly become a trend. This review presents several biomarkers of esophageal cancer, including chemotherapy-related biomarkers and targeted drug-related biomarkers, and the correlation of these biomarkers with drug response.
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