Expression And Clinical Significance Of BMAL1? Per2?Notch1 And GSK-3? In Colorectal Adenocarcinoma

Objective: To investigate the expression and correlation of BMAL1,Per2,Notch1,GSK-3? proteins in para-cancerous tissue,colorectal adenoma tissue and colorectal adenocarcinoma tissues.Analyzing the relationship between these four indicators and the characteristics of clinical cases of colorectal cancer.Methods:qRT-PCR technique was used to detect the expreesion levels of BMAL1,Per2,Notch1 and GSK-3? in 11 colorectal adenocarcinoma tissues and its para-carcinoma tissues.The expression levels of BMAL1,Per2,Notch1 and GSK-3? were detected in 30 colorectal tissues?50 colorectal adenocarcinoma tissues and its para-carcinoma tissues by immunohistochemistry.Further analyze the correlation between the four indicators and the relationship with the characteristics of clinical cases.Results: PCR results showed that the expression level of BMAL1,Per2 in colorectal cancer were significantly lower than that in paired adjacent tissues,and the difference was statistically significant(P < 0.05),while the expression levels of Notch1 and GSK-3?,respectively were not statistically significant(P>0.05).Immunohistochemical results showed that BMAL1,Per2,Notch1,GSK-3? were expressed in paracancer tissues,adenoma tissues and adenocarcinoma tissues.The positive rates of BMAL1 were 74.0%(37/50),46.7%(14/30),12.0%(6/50),respectively.The positive rates of Per2 were 70.0%(35/50),43.3%(13/30),16.0%(8/50),respectively.The positive rates of Notch1 were48.0%(24/50),70%(21/30),90.0%(45/50),respectively.The positive rates of GSK-3?were 52.0%(26/50),83.3%(25/30)and 86.0%(43/50),respectively.The positive rates of BMAL1 and Per2 in colorectal adenocarcinoma were lower than those in adenoma and para-carcinoma,while the positive rates of Notch1 and GSK-3? were higher than those in adenoma and para-carcinoma.The positive expression of four indicators was compared in paracancer,adenoma and adenocarcinoma groups.There were statistically significantdifferences with the above indexes between para-cancerous and adenocarcinoma group,the para-cancerous and the adenoma group,adenocarcinoma and the adenoma group(P<0.05).Meanwhile,the differences of BMAL1 and Per2 expression in adenoma group and adenocarcinoma group were statistically significant(P<0.05),while there was no significant difference in Notch1 and GSK-3? between the two groups(P>0.05).The expression of BMAL1 had nothing to do with gender,age,expression site,invasion depth,tumor size,and pathological type(P>0.05),but correlated with lymph node metastasis and TNM stage(P< 0.05).The higher the lymph node metastasis and TNM stage,the higher the expression of BMAL1.The expression level of Per2 was only associated with tumor pathological types(P < 0.05),and mucinous adenocarcinoma had a higher positive level of Per2 expression than tubular adenocarcinoma.The expression of Notch1 was associated with lymph node metastasis and TNM stage(P< 0.05).With lymph node metastasis,the higher the TNM stage,the higher the positive expression of Notch1.The expression of GSK-3? protein was only correlated with the pathological type of tumor(P<0.05),and tubular adenocarcinoma had a higher degree of positive GSK-3? expression than mucinous adenocarcinoma.Correlation analysis among various indicators in colorectal adenocarcinoma showed that the expressions of GSK-3? was negatively correlated with Per2(r=-0.291,P<0.05),and positively correlated with Notch1(r=0.285,P<0.05),and the expressions of BMAL1 is positively correlated with the expressions of Per2(r=0.332,P<0.05).Conclusion:1.The expression of BMAL1 and Per2 were down-regulated in human colorectal adenocarcinoma,colorectal adenoma,paracancerous tissue,while the expressions of Notch1 and GSK-3? were up-regulated.Their abnormal expression may be associated with the onset of colorectal adenocarcinoma.2.The expressions of BMAL1 and Notch1 were correlated with lymph node metastasis and TNM stage,while the expressions of Per2 and GSK-3? were correlated with tumor pathological types.The combined testing of Notch1 and BMAL1 may be helpful in evaluating the metastasis and prognosis of patients with colorectal adenocarcinoma.3.In colorectal adenocarcinoma tissue,the expressions of GSK-3? is negatively correlated with the expressions of Per2,and positively correlated with the expressions of Notch1,and the expressions of BMAL1 is positively correlated with the expressions of Per2.