Abstract

Nestin is associated with neoplastic transformation. However, the mechanisms by which nestin contributes regarding invasion and malignancy of gastric adenocarcinoma (GAC) remain unknown. Recent studies have shown that the epithelial-mesenchymal transition (EMT) is important in invasion and migration of cancer cells. In the present study, we aimed to investigate the expression of nestin and its correlation with EMT-related proteins in GAC. The expression of nestin and EMT-related proteins was examined in GAC specimens and cell lines by immunohistochemistry and Western blotting. Clinicopathological features and survival outcomes were retrospectively analyzed. Positive nestin immunostaining was most obviously detected in the cytoplasm, nucleus or both cytoplasm and nucleus of tumor cells in 19.2% (24/125) of GAC tissues, which was significantly higher than that in normal gastric mucosa tissues (1.7%, 1/60) (p=0.001). Nestin expression was closely related to several clinicopathological factors and EMT-related proteins (E-cadherin, vimentin and Snail) and displayed a poor prognosis. Interestingly, simultaneous cytoplasmic and nuclear nestin expression correlated with EMT-related proteins (E-cadherin, vimentin and Snail) (p<0.05) and lymph node metastasis (p=0.041) and a shorter survival time (p<0.05), but this was not the case with cytoplasmic or nuclear nestin expression. Nestin, particularly expression in both cytoplasm and nucleus, might be involved in regulating EMT and malignant progression in GAC, with potential as an unfavorable indicator in tumor diagnosis and a target for clinical therapy.

Highlights

  • Gastric cancer is the fourth most common malignant disease and the second most frequent cause of cancerrelated death worldwide (Takaishi et al, 2009)

  • Positive nestin immunostaining was most obviously detected in the cytoplasm, nucleus or both cytoplasm and nucleus of tumor cells in 19.2% (24/125) of gastric adenocarcinoma (GAC) tissues, which was significantly higher than that in normal gastric mucosa tissues (1.7%, 1/60) (p=0.001)

  • We examined the expression of nestin in 125 human primary GAC samples using immunohistochemical analyses

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Summary

Introduction

Gastric cancer is the fourth most common malignant disease and the second most frequent cause of cancerrelated death worldwide (Takaishi et al, 2009). The epithelial-mesenchymal transition (EMT) is a critical biological process by which epithelial cells lose their polarized, epithelial morphology and acquire a mesenchymal-like phenotype It is characterized by the downregulation of epithelial protein expression, such as E-cadherin, and the upregulation of mesenchymal protein expression, such as vimentin and fibronectin (Luo et al., 2012; Zhu et al, 2013). The mechanisms by which nestin contributes regarding invasion and malignancy of gastric adenocarcinoma (GAC) remain unknown. Nestin expression was closely related to several clinicopathological factors and EMT-related proteins (E-cadherin, vimentin and Snail) and displayed a poor prognosis. Simultaneous cytoplasmic and nuclear nestin expression correlated with EMT-related proteins (E-cadherin, vimentin and Snail) (p

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