Helicobacter pylori-induced epithelial-mesenchymal transition, a potential role of gastric cancer initiation and an emergence of stem cells.

We know little concerning the expression of transforming growth factor-β1 (TGF-β1) and TGF-β1-induced epithelial-mesenchymal transition (EMT) markers in gastric mucosa and their changes after eradication of Helicobacter pylori infection have not yet been clarified. In the present study, we compared the time course of messenger RNA (mRNA) expression of TGF-β1 and five EMT markers (Twist, Snail, Slug, vimentin and E-cadherin) in 111 controls, 55 patients with gastric dysplasia and 71 patients with early gastric cancer, following eradication of H.pylori. mRNA levels in non-cancerous gastric mucosa were measured using quantitative real time-polymerase chain reaction and the histologic findings of gastric mucosa were compared before and after eradication. The average duration of follow-up was 46.7 months (6.0-112.4). The levels of TGF-β1, Twist, Snail, Slug and vimentin mRNA, in addition to levels of CD44 detected by immunohistochemistry, showed all up-regulation in patients with dysplasia or early gastric cancer compared with controls (P < 0.05); moreover, the mRNA levels of E-cadherin, an epithelial marker, were decreased in these patients compared with the control group (P < 0.001). Eradication of H.pylori reduced the expression of TGF-β1, Twist, Snail, Slug and vimentin mRNA (P-value for slope <0.001), as well as the immunohistochemical expression of CD44 (P = 0.014), whereas it enhanced the expression of E-cadherin (P-value for slope < 0.05). Thus, H.pylori infection may trigger the TGF-β1-induced EMT pathway and the emergence of gastric cancer stem cells (CSCs). Its eradication may prevent the carcinogenesis of gastric cancer by inhibiting these two pathways.

Choi YJ ，Kim N ，Chang H ，Lee HS ，Park SM ，Park JH ，Shin CM ，Kim JM ，Kim JS ，Lee DH ，Jung HC ... -  《-》

The clinical significance of vimentin-expressing gastric cancer cells in bone marrow.

Iwatsuki M ，Mimori K ，Fukagawa T ，Ishii H ，Yokobori T ，Sasako M ，Baba H ，Mori M ... -  《-》

TWIST1 and SNAI1 as markers of poor prognosis in human colorectal cancer are associated with the expression of ALDH1 and TGF-β1.

Kim YH ，Kim G ，Kwon CI ，Kim JW ，Park PW ，Hahm KB ... -  《-》

Combination of epithelial-mesenchymal transition and cancer stem cell-like phenotypes has independent prognostic value in gastric cancer.

Epithelial-mesenchymal transition-related proteins have been suggested to interact with each other in various cancers and be associated with the aggressive behavior of cancer. To demonstrate the clinical significance of epithelial-mesenchymal transition and stem cell-like phenotypes in gastric cancer, we performed immunohistochemistry for 5 epithelial-mesenchymal transition-related proteins, including Snail-1, ZEB-1, E-cadherin, vimentin, and β-catenin, and the gastric cancer stem cell marker CD44 in 276 consecutive primary gastric cancers and 54 matched lymph node metastases. Loss of E-cadherin expression and aberrant expression of vimentin were significantly associated with aggressive clinicopathologic features. The expression of epithelial-mesenchymal transition-related proteins was closely related to each other in gastric cancer. The known gastric cancer stem cell maker, CD44, was significantly associated with the protein expression of Snail-1, ZEB-1, and E-cadherin (P < .05). Univariate survival analysis was performed for the 6 proteins included in this study to find the best combination for predicting patient outcome. Protein expression of Snail-1, vimentin, E-cadherin, and CD44 resulted in the lowest P value using the Kaplan-Meier method (P < .001). This combination of proteins was significantly associated with advanced pT stage, lymph node metastasis, vascular invasion, and undifferentiated histologic type in a high-risk group (P < .001) and predicted disease-free survival independent of pTNM stage and histologic differentiation (P = .029). However, the acquired mesenchymal phenotype of gastric cancer cells at the primary site was restored to an epithelial phenotype in lymph node metastases. A combination of epithelial-mesenchymal transition and stem cell-like phenotypes is an important predictor of aggressive biologic behavior and has an independent prognostic value in predicting outcomes of primary gastric cancer.

Ryu HS ，Park DJ ，Kim HH ，Kim WH ，Lee HS ... -  《-》

Downregulated Expression of E-cadherin and TP53 in Patients with Gastric Diseases: the Involvement of H. pylori Infection and Its Virulence Markers.

Ferraz MA ，Zabaglia LM ，Pereira WN ，Orcini WA ，de Labio RW ，Caleman Neto A ，Wisnieski F ，Calcagno DQ ，Santos LC ，Assumpção PP ，Burbano RR ，Artigiani R ，Smith Mde A ，Payão SL ，Rasmussen LT ... -  《-》