High-mobility-group A2 over-expression in gastric cancers is indicative of a poor prognosis based on a relationship to the epithelial-mesenchymal transition

Aim/Background

The aim of the present study was to use surgical gastric cancer specimens and patient clinicopathological data to investigate the clinical significance of HMGA2 overexpression in gastric cancer. In addition, the mechanism by which HMGA2 expression acts on the gastric cancer and the association between that mechanism and EMT were analyzed in an in vitro study using a gastric cancer cell line.

Methods

The present study assessed the clinical and molecular effects of HMGA2 with the malignant tissues of 170 patients with gastric cancer and gastric cancer cells expressing HMGA2. HMGA2 expression was determined using immunohistochemistry and analyzed with respect to the clinicopathological data of patients with this tumor. In the gastric cancer cell line MKN28, in which HMGA2 was knocked down by two different short-hairpin RNAs, trans-well migration and invasion assays were conducted and western blotting was used to detect the altered expression of EMT markers.

Results

In patients with gastric cancer, HMGA2 overexpression correlated with tumor progression and was indicative of a significantly worse overall survival. Migration and invasion assays using HMGA2-knockdowned MKN28 cells showed a reduction in cell migration and invasion. The up-regulation of E-cadherin, an epithelial marker, and the down-regulation of N-cadherin, a mesenchymal marker were observed in HMGA2-knockdowned cells. In addition, expression of the transcriptional factors Snail and Zeb1 and of the EMT-pathway molecule ß-catenin were decreased.

Conclusions

HMGA2 overexpression, through its relationship to EMT, thus seems to aggravate invasion and metastasis in gastric cancer. It may therefore serve as a predictive marker in determining the clinical outcome of patients with gastric cancer and offer a promising therapeutic target.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.