Expression Of CDX2 And Reg? And Their Correlationship In Human Gastric Cancer

Objective:Gastric cancer is a common malignant tumor of the digestive system,which poses a serious threat to human health.Currently,research has shown that high expression of Reg IV promotes the occurrence and development of gastric cancer.The ectopic expression of CDX2 is closely related to the occurrence and development of gastric cancer.The expression of CDX2 was highly related with Reg IV in various other types of tumors,while the correlation between the expression of CDX2 and Reg IV in gastric cancer remains untested,and the molecular mechanism of how CDX2 affect gastric cancer cells is still unclear.The purpose of this study was to investigate the expression and correlation of CDX2 and Reg IV in gastric cancer by detecting their transcription and protein levels in gastric cancer tissues and adjacent tissues,and to further investigate the regulatory relationship and function of CDX2 and Reg IV in AGS and MKN-45 cells.Methods:Immunohistochemistry and real-time PCR were used to examine the expression of CDX2 and Reg IV at the mRNA and protein levels in 102 paraffin-embedded samples of gastric cancer,30 corresponding paraffin-embedded adjacent tissues samples and 93 fresh gastric cancer tissue samples,and to analyze correlation between the two genes.CDX2 and Reg IV genes were silenced or overexpressed in AGS and MKN-45 gastric cancer cells,real-time PCR and Western blot were used to examine CDX2 and Reg IV expression at the mRNA and protein levels,and to analyze regulatory relationship between the two genes.Wound-healing and Transwell assays were used to examine migration and invasion in AGS and MKN-45 cells following CDX2 silencing or overexpression.Results:(1)Immunohistochemical results showed that the expression of Reg IV in cancer tissues was significantly higher than that in adjacent tissues(P = 0.029),while the expression of CDX2 in cancer and adjacent tissues was not significantly different(P = 0.435).Moreover,positive relation between CDX2 and Reg IV was observed in both protein(r = 0.334,P = 0.001)and mRNA levels(r = 0.387,P = 0.000).(2)In AGS cells,after overexpression of the CDX2 gene,the mRNA and protein expression levels of CDX2 and Reg IV increased significantly;after silencing the expression of the CDX2 gene,the mRNA and protein expression levels of CDX2 and Reg IV decreased significantly;After overexpression of the Reg IV gene,the mRNA and protein levels of Reg IV increased significantly,and the mRNA and protein levels of CDX2 did not change significantly compared with the control group;after the expression of Reg IV was silenced,the mRNA and protein expression levels of Reg IV and CDX2 were decreased significantly compared with the control group.(3)In MKN-45 cells,after overexpressing the CDX2 gene,the mRNA and protein expression levels of CDX2 and Reg IV significantly increased;after silencing CDX2 gene,the mRNA and protein expression levels of CDX2 and Reg IV significantly decreased;after overexpression of the Reg IV gene,the mRNA and protein levels of Reg IV increased significantly,but the mRNA levels of CDX2 decreased significantly compared to the control group.There was no significant change in protein levels;after silencing Reg IV gene,the mRNA and protein levels of Reg IV were significantly increased.The mRNA and protein levels of CDX2 did not change significantly compared with the control group.(4)The results of Wound-healing and transwell assays showed that the migration and invasion ability of AGS and MKN-45 cells were significantly enhanced when CDX2 was overexpressed;consistently,silencing CDX2 significantly weakened the migration and invasion ability of AGS and MKN-45.Conclusion:The expression of CDX2 and Reg IV are positively correlated in gastric cancer.CDX2 promotes the migration and invasion of gastric cancer cell lines AGS and MKN-45 by enhancing Reg IV expression.