Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma.
ABSTRACT Epithelial-mesenchymal transition (EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is known to be involved in the progression and metastasis of various cancers. The aim was to evaluate the expression of EMT-related proteins in gastric carcinoma (GC).
The expression of nine EMT-related proteins in the GC tissues of 598 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of EMT-related proteins. Loss of epithelial protein and/or acquisition of the expression of mesenchymal proteins were observed in GC. These protein alterations were associated with diffuse type histology, advanced stage and poor patient outcome, respectively. Subjects were divided into three groups according to degree of EMT-related protein alteration. Increases in alteration of EMT-related protein were found to be significantly associated with poorly differentiated histology, higher pTNM stage and unfavourable outcome. Multivariate analysis showed that alterations in the expression of EMT-related proteins were independently associated with poor prognosis.
Loss of epithelial proteins and/or the acquisition of mesenchymal proteins are associated with poorly differentiated histology, advanced stage and poor outcome in GC. The awareness and inhibition of EMT offer a promising target for prevention of metastatic progression and invasion.
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ABSTRACT: Helicobacter pylori, a Gram-negative, microaerophilic bacterium found in the stomach, is assumed to be associated with carcinogenesis, invasion and metastasis in digestive diseases. Cytotoxin-associated gene A (CagA) is an oncogenic protein of H. pylori that is encoded by a Cag pathogenicity island related to the development of gastric cancer. The epithelial-mesenchymal transition (EMT) is the main biological event in invasion or metastasis of epithelial cells. H. pylori may promote EMT in human gastric cancer cell lines, but the specific mechanisms are still obscure. We explored the underlying molecular mechanism of EMT induced by H. pylori CagA in gastric cancer. In our article, we detected gastric cancer specimens and adjacent non-cancerous specimens by immunohistochemistry and found increased expression of the EMT-related regulatory protein TWIST1 and the mesenchymal marker vimentin in cancer tissues, while programmed cell death factor 4 (PDCD4) and the epithelial marker E-cadherin expression decreased in cancer specimens. These changes were associated with degree of tissue malignancy. In addition, PDCD4 and TWIST1 levels were related. In gastric cancer cells cocultured with CagA expression plasmid, CagA activated TWIST1 and vimentin expression, and inhibited E-cadherin expression by downregulating PDCD4. CagA also promoted mobility of gastric cancer cells by regulating PDCD4. Thus, H. pylori CagA induced EMT in gastric cancer cells, which reveals a new signaling pathway of EMT in gastric cancer cell lines.PLoS ONE 01/2014; 9(8):e105306. · 3.53 Impact Factor
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ABSTRACT: Background and aim: The discs large 1 of Drosophila (DLG1) is a cell junction-localized protein that is required for the maintenance of cyto-architectural stability and alteration of DLG1 may be related to development of epithelial neoplasm. Methods: To determine DLG1 expression in human papillomavirus-related carcinogenesis, DLG1 expression in normal larynx (NL), laryngeal nodule (LN), laryngeal papilloma (LP), and invasive squamous cell carcinoma of larynx (SQCC) was investigated using immunohistochemistry. Results: In LN, the expression pattern of DLG1 was similar to NL showing cytoplasmic expression of basal and suprabasal cells except suprabasal membranous staining, which is observed in NL. In regard to basal cell expression, unlikely NL and LN, and the basal cells of most LPs did not express DLG1. In SQCC, the cancer cells of surface area showed strong cytoplasmic and membranous staining patterns of DLG1 in most SQCCs, whereas cells of deep invasive edge (IE) demonstrated weak cytoplasmic patterns without membranous staining. This expression pattern of DLG1 was similar to that of E-cadherin. Conclusions: Weak expression of DLG1 in IE of SQCC with a pattern similar to E-cadherin suggests that the perturbation of DLG1 as cell junction-localized cyto-architectural protein may be associated with progression of invasiveness.Basic and Applied Pathology 12/2011; 4(4).
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ABSTRACT: To evaluate the effect of β-catenin immunohistochemical expression on the prognosis of gastric cancer (GC).World journal of gastroenterology : WJG. 09/2014; 20(34):12313-21.