| Background and PurposeGastric cancer (GC) is the fourth most common malignancy and the second leading cause of cancer-related mortality worldwide. When dignoised, most of the gastric cancer patients are moderate-advanced stage due to lack of the early symptoms,so the effect of treatment as well as prognosis of gastric cancer is poor.Recently, Cancer stem cells have been proposed to be responsible for cancer tumorigenicity.The sternness factors Sox-2, Oct-4were associated with induced pluripotent stem cells, suggesting a correlation between these sternness factors and cancer stem cells.These factors were not only associated with cell differentiation but also associated with carcinogenesis and tumor progression. E-cad is a transmembrane cell adhesion molecules that mediate cell-cell interactions and are important for maintenance of epithelial cell integrity.β-cat plays two important functions. It is involved in cell adhesion, binding E-cad to the actin cytoskeleton via α-catenin, β-cat is also a key element in cell signaling via the WNT/wingless pathway.In the malignant neoplasms, the abnormal expression of E-cad and P-cat may lead to the loss of their adhesion function which may contribute to loss of contact inhibition.With this way, the tumor cells fall off from the primary tumor, getting the ability of invasion and metastasis, thus play an important role in carcinogenesis and tumor progression.In this study, we detect the expression of these five proteins, and investigate the clinical significance of these four protenins in the gastric cancer.Materials and MethodsThe expression of Oct-4, sox-2and E-cad, β-cat were detected by the Envision immunohistochemical method in69cases of gastric cancer, Theχ2test was used to determine the significance of the differences between the clinicopathological features and the expression of Oct-4, Sox-2, E-cad, β-cat. Survival curves were plotted according to Kaplan-Meier survival curve method, and the logistic regression model was used to measure the differences of disease free survival.Last, Correlations between variable factors were calculated by Sperman correlation coefficients., multivariate survival analyses were performed with the Cox regression model. In all of the tests, a P value<0.05was defined as statistically significant. The SPSS10.0software program was used for the analyses.Result(1) Oct4expression in GC tumors correlated with their differentiation status (P<0.05), but not with patient age or gender, tumor location, depth of invasion, lymph node invasion and distant metastasis(P>0.05).The expression status of Sox-2was not associated with any clinicopathologic factor(P>0.05),including gender, age, tumour location,differentiation, depth of tumour invasion, lymph node metastasis and distant metastasis. The DFS of patients with Sox2-positive tumors or Oct4-positive tumors was significantly(P<0.05) worse than that of patients with Sox2-negative or Oct3/4-positive tumors, respectively. Furthermore, patients with co-expression of Oct-4and Sox-2in the gastric cancer had significantly worse desease free surviva (P<0.05).(2) E-cad or β-cat expression had a positive correclation with lymph node metastasis, differentiation and distant metastasis(P<0.05), and either of these two marker were not associated with other clinicopathologic factor(P>0.05). The disease free survival of Sox2-positive or Oct4-positive patients was significantly (P<0.05) lower than that of Sox2-negative or Oct4-positive patients. The disease free survival of double-positive patients was significantly (P<0.05) lower than that of single-positive and double-negative patients.(3) With the multivariate survival analyses of69gastric cancer patients, the expression of Sox-2,(3-cat may be independent prognostic factors of gastric cancer.(4) During the69patients, the expression of Sox-2and β-cat were positively related with Oct-4expression (P<0.05), The expression of Sox-2was not associated with E-cad and p-cat (P>0.05), There is a positive correlation between the expression of E-cad and β-cat(P<0.05).Concolusion(1) Univariate analyses show that the expression of all these4protenins were negatively correlated to the DFS. A multivariate survival analysis Was performed with the Coxregression model identified that the expression status of Sox-2and β-cat were two independent predictive factors for prognoses of gastric cancer patients after operation. The expression of Oct-4in gastric cancers was associated with differentiation, both E-cad and β-cat in gastric cancers had remarkable correlations to the depth of tumor invasion, cell differentiation and distant metastasis.(2) Both β-cat and Sox-2expression were positive correlated to the expression of Oct-4. Also, the expression of E-cad were positive correlated to the expression of β-cat. These results indicate that Oct-4, an important biomarker, combining with Sox-2and E-cad, may play an important role in the development and metastasis of gastric cancer. |
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