Objective To investigate the prognostic value of epithelial-mesenchymal transition (EMT) related proteins (Snail, E-cadherin, and N-cadherin) in gastric cancer and its relationship with tumor initiating cells (TICs) marker (CD133). Methods The expressions of EMT-related proteins and CD133 protein in the gastric cancer tissues and normal gastric mucosa tissues adjacent to gastric cancer were detected by Western blot method. The relations between the expressions of EMT-related factors proteins and CD133 protein and the clinicopathologic characters were analyzed. The correlations between EMT-related factors and CD133 were analyzed by Spearman. The correlations between EMT-related factors expressions and CD133 expression and survival were analyzed by Kaplan-Meier method and Log-rank test. Results ① The protein expression levels of Snail, N-cadherin, and CD133 in the gastric cancer tissues were significantly higher than those in the normal gastric mucosa tissues adjacent to gastric cancer (Snail:0.599±0.114 versus 0.259±0.108, P=0.020;N-cadherin:0.754±0.154 versus 0.329±0.134, P=0.001;CD133:0.635±0.119 versus 0.485±0.116, P=0.029), while the protein expression level of E-cadherin was lower than that in the normal gastric mucosa tissues adjacent to gastric cancer (0.378±0.123 versus 0.752±0.156, P=0.003).② The expression levels of Snail and N-cadherin in the gastric cancer patients with vascular invasion, lymphatic vessel invasion,N3 lymph node metastasis, diameter more than 5 cm, and Ⅲ+Ⅳ staging were significantly higher than those in the patients without vascular invasion, lymphatic vessel invasion, N0-N2 lymph node metastasis, diameter less than 5 cm, andⅠ+Ⅱ staging(P<0.05), while E-cadherin protein expression was lower than that in the patients without vascular invasion, lymphatic vessel invasion, N0-N2 lymph nodes metastasis, andⅠ+Ⅱstaging (P<0.05). The expression levels of CD133 in the gastric cancer patients with lymphatic vessel invasion, diameter more than 5 cm, and Ⅲ+Ⅳ staging were significantly higher than those in the patients without lymphatic vessel invasion, diameter less than 5 cm, andⅠ+Ⅱ staging (P<0.05). ③The Snail and N-cadherin protein expressions were significantly positive correlated with CD133 protein expression, respectively (rs=0.278, P=0.048;rs=0.406, P=0.003), while E-cadherin protein expression was significantly negative correlated with CD133 protein expression (rs=-0.504, P=0.000).④ The survival time in the patients with lower expressions of Snail, N-cadherin, and CD133 were significantly longer than those in the patients with higher expressions of Snail, N-cadherin, and CD133 (P<0.05). The combination of Snail, N-cadherin, E-cadherin, and CD133 could effectively predict survival. Conclusions There is a significant correlation between EMT and gastric cancer TICs, and which are correlated with aggressive clinicopathologic features of gastric cancer. The combination of Snail, E-cadherin, N-cadherin, and CD133 may be effectively predict the prognosis of gastric cancer patients.
Objective To summarize the relationships between chemokines or chemokine receptors, especially CCL19/CCL21-CCR7 and CXCL12-CXCR4 axis and occurrence and development of gastric cancer. Methods Domestic and international publications online involving the relationships between chemokines, chemokine recepotors and gastric cancer in recent years were collected and reviewed. Results By regulating the microenvironment of the growth of gastric cancer, CCL19/CCL21-CCR7 played an important role in lymph node metastasis and CXCL12-CXCR4 axis played a key role in the development of peritoneal carcinomatosis. CCR7 might function as a specific prognostic marker for lymph node metastasis of gastric cancer. Blocking the CXCL12-CXCR4 axis might be useful for the future development of a more effective therapeutic strategy for gastric cancer involved in peritoneal dissemination. Conclusions Chemokines and chemokine receptors promote the evolution of gastric cancer in variable ways, so the mechanisms of which should be comprehended to provide a theoretical basis for the future treatment. As new therapeutic targets, chemokines and chemokine receptors have a prosperity for the clinic evaluation and treatment of gastric cancer.
Objective To investigate the expression of transcription factor e2f-1 in the different development stages of gastric cancer, the relationships between clinicopathologic characteristics and e2f-1 expression status, as well as its influences on the prognosis. Methods The operative samples from primary lesion of 121 patients who underwent radical resection for gastric cancer were detected by SABC immunohistochemical staining. The relationships of e2f-1 expression with clinicopathologic characteristics and with the prognosis were observed by univariate, multivariate and relative analyses. Results The total positive expression rate of e2f-1 in all patients was 38.8% (47/121). With the advancement of gastric cancer, the level of e2f-1 expression in TNMⅠ-Ⅳ stage was gradually decreased (r=-0.320, Plt;0.05): Ⅰa stage with 62.5% (10/16), Ⅰb with 47.1% (8/17), Ⅱwith 55.0% (11/20), Ⅲa with 40.0% (8/20), Ⅲb with 27.3% (6/22), Ⅳ with 15.4% (4/26). The expression of e2f-1 was significantly negative correlated with tumor diameter, depth of infiltration, lymph node metastasis ratio, and N stage (Plt;0.05). The multivariate analysis revealed that either histology type, or survival time was respectively an independent factor for e2f-1 expression (Plt;0.05). Log-Rank test showed the relative factors to survival included N stage, tumor diameter, tumor position, lymph node metastasis ratio, depth of infiltration, and TNM stage (Plt;0.05). Cox survival analysis found that both of later N stage and e2f-1 higher expression were independent prognostic factors (Plt;0.05). The higher e2f-1 expression was related to a poor survival in TNM stageⅠand Ⅱ patients (r=-0.304, Plt;0.05), the prognosis of patients with e2f-1 positive expression was worse than that of patients with negative expression (χ2=13.437, Plt;0.05), and there was no statistic relationship between the expression of e2f-1 and prognosis in stage Ⅲ and Ⅳ patients (Pgt;0.05). Conclusions e2f-1, as a useful marker, seems to be an indication for the malignant behavior in relatively earlier gastric cancer, in which the e2f-1 positive expression shares a significantly poor survival. And the lower expression of e2f-1 has been identified in later advanced gastric cancer, the more malignances in advanced gastric cancer might associate with a lower expression of e2f-1.