| Objectives:The E-cadherin/catenin complex not only mediates cell adhesion,but also participates in cell signaling transduction directly or indirectly,which plays an important role in tumorigenesis,development and metastasis.YAP1,as a pivotal downstream protein in the Hippo pathway,can induce the activation of multiple target genes related to invasion?metastasis?proliferation and apoptosis.this research aimed to investigate the expression of E-cad??-cat??-cat?p120-cat and YAP1 protein in colorectal cancer tissues and their clinical significance.Methods:We Collected colorectal cancer cases by the inclusion criteria strictly,and used immunohistochemistry to detect the expression of E-cad??-cat??-cat?p120-cat and YAP1 proteins in colorectal cancer tissue and normal intestinal mucosal tissue 2 cm adjacent to cancer.Chi-square test was used to analyze the differences of E-cad??-cat??-cat?p120-cat and YAP1 expression between colorectal cancer tissue and normal intestinal mucosal tissue and their relationships with clinicopathological parameters of colorectal cancer.Kaplan-Meier survival analysis and Cox proportional harzard model were used to analyze the clinicopathological parameters and the effect of E-cad??-cat??-cat?p120-cat and YAP1 on the prognosis of colorectal cancer patientsResults:1.E-cad??-cat??-cat?p120-cat was highly expressed in the normal intestinal mucosal gland epithelial cell membrane of 2 cm adjacent to cancer,but lowly expressed in the cell membrane or ectopicly expressed in plasm or nuclear of colorectal cancer cells;YAP1 lowly expressed in the normal intestinal mucosal gland epithelium,but highly expressed or nuclear ectopic expressed in colorectal cancer cells2.The relationships between five proteins and clinicopathological parameters:?The E-cad's low expression or nuclear/plasmic ectopic expression was associated with the degree of colorectal cancer differentiation(P=0.000).The worse tumor differentiation,the rate of low E-cad's expression or nuclear/plasmic ectopic expression was higher.?The ?-cat's low or nuclear/plasmic ectopic expression was associated with colorectal cancer's pT stage(P=0.032),degree of differentiation(P=0.000),and lymph node metastasis(P=0.008).The ?-cat's low expression or nuclear/plasmic ectopic expression rate increased with the increasing of pT stage.The worse tumor differentiation,the rate of ?-cat's low expression or nuclear/plasmic ectopic expression is higher.The ?-cat's lower expression or nuclear/plasmic ectopic expression rate was higher in the lymph node metastasis group than in the lymph node non-metastasis group.The ?-cat's low expression or nuclear/plasmic ectopic expression rate was higher in the group which happened distant metastasis.? The?-cat's low or nuclear/plasmic ectopic expression was associated with tumor differentiation(P=0.002),lymph node metastasis(P=0.017).The worse tumor differentiation,the(?-cat's low expression or ectopic expression ratio was higher.In the lymph node metastasis group,(?-cat's low expression or nuclear/plasmic ectopic expression rate increased comparing with the non-metastatic group.?The p120-cat's low or nuclear/plasmic ectopic expression was associated with patient's age(P=0.003),tumor differentiation(P=0.010)and lymph node metastasis(P=0.005).The p120-cat's low or nuclear/plasmic ectopic expression rate of the group which age was<60 was higher than age?60.The worse tumor differentiation,it was easier to show p120-cat expressing lowly or ectopicly.In the lymph node metastasis group,p120-cat's low expression or nuclear/plasmic ectopic expression rate was higher.?The YAP1's high expression and nuclear ectopic were associated with tumor differentiation(P=0.013),pT stage(0.006),and distant metastasis(P=0.023).The worse tumor differentiation,the YAP1's high expression or ectopic expression rate was higher.The higher the pT stage,the YAP1's high expression or ectopic expression rate was higher.The rate of YAP 1 high or ectopic expression in the distant metastasis group was higher.3.E-cad is negative to YAP 1(P=0.019,R=-0.198),?-cat is negative to YAP 1(P=0.000,R=-0.361),?-cat is positive to p120-cat(P=0.000,R=0.394)4.The clinicopathological parameters affecting the prognosis of colorectal cancer included tumor size,degree of differentiation,pT stage,lymph node metastasis,distant metastasis.As proteins,?-cat and YAP1 affected the prognosis of colorectal cancer.5.The negative expression of E-cad and YAP1 was associated with distant metastasis(P=0.049)and overall survival(P=0.002)in colorectal cancer.When E-cad was low or ectopic expression and YAP1 was high or nuclear ectopic expression,the risk of distant metastasis and death in colorectal cancer patient enlarged.The negative expression of ?-cat and YAP1 was associated with lymph node metastasis(P=0.033),distant metastasis(P=0.047),and overall survival(P=0.002).When ?-cat was low or ectopic expression,YAP1 was high or nuclear ectopic expression,colorectal cancer had a higher risk of lymph node metastasis,distant metastasis,and death.The combined expression of ?-cat and p120-cat was associated with lymph node metastasis(P=0.000),distant metastasis(P=0.012)and overall survival(P=0.002).When both ?-cat and p120-cat showed low or ectopic expression,colorectal cancer had a higher risk of lymph node metastasis,distant metastasis and death.Conclusions:1.The expression of E-cad??-cat??-cat?p120-cat and YAP1 in colorectal cancer and normal intestinal mucosa was different and statistically significant.2.E-cad??-cat??-cat and p120-cat and YAP1's expression were associated with colorectal clinicopathological parameters,such as tumor size?pT stage?degree of differentiation?lymph node metastasis?distant metastasis,etc.3.Tumor size,degree of differentiation,pT stage,lymph node metastasis and distant metastasis were the influencing factors of poor prognosis in colorectal cancer patients.?-cat's low or ectopic expression,YAP1's high expression or nuclear localization expression are the affecting factors of poor prognosis in colorectal cancer patients.4.E-cad was negative to YAP1.?-cat was negative to YAP1.?-cat was positive to p 120-cat.The negative expression of E-cad and YAP1 was associated with distant metastasis of colorectal cancer and overall survival of patients.The negative expression of ?-cat and YAP1 was associated with lymph node metastasis,distant metastasis and overall survival of patients.The combined expression of ?-cat and p120-cat was associated with lymph node metastasis,distant metastasis,and overall survival of patients.5.E-cad and ?-cat may be the negative regulators to YAP1,which influence the progressment of colorectal cancer by regulating YAP1's expressing localization. |
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