Expression And Clinical Significance Of CDX2 And HNF4? In Gastric Cancer

Gastric intestinal metaplasia refers to a pathological process in which gastric epithelial cells are replaced by intestinal epithelial cells,and is also an important precancerous lesion of gastric cancer,especially intestinal type gastric cancer.The appearance of intestinal metaplasia promotes the occurrence and development of gastric cancer.Therefore,the research on intestinal metaplasia has become the top priority in current gastric cancer research.Caudal type homeobox 2?CDX2?is an intestinal-specific transcription factor that can induce the appearance of gastric intestinal metaplasia after overexpression and is a marker molecule for intestinal metaplasia.Hepatocyte nuclear factor 4??HNF4??belongs to the nuclear receptor superfamily and is divided into P1-HNF4?and P2-HNF4?.Studies have found that abnormal expression of HNF4?can induce the production of intestinal columnar epithelium.Both of them were significantly associated with the occurrence and development of intestinal metaplasia and gastric cancer.Previous experiments in this laboratory confirmed that there was a mutual regulation relationship between CDX2 and HNF4?.Therefore,this experiment will analyze the correlation between CDX2,P1-HNF4?and P2-HNF4?in the process of gastric cancer on the basis of previous experiments.Objective:To investigate the positive expression of CDX2 and HNF4?in gastric cancer tissues,and to analyze their relationship between CDX2 and HNF4?and clinicopathological factors of gastric cancer patients and their prognosis.Methods:Immunohistochemical staining?ABC?was used to detect the expression of CDX2,P1-HNF4?and P2-HNF4?in gastric mucosa of 50 patients with chronic gastritis,86 intestinal metaplasia and 97 patients with gastric cancer.Combined with the expression intensity and the number of positive cells,the relationship between the expression level and the clinician pathological parameters was analyzed.Combined with the 9-year follow-up data of gastric cancer patients,the reference significance of CDX2 and HNF4?expression in the prognosis evaluation of gastric cancer patients was evaluated.At the same time,the correlation between CDX2 and P1-HNF4?and P2-HNF4?expression in the above gastric mucosa specimens was analyzed.Results:CDX2,P1-HNF4?and P2-HNF4?were mainly expressed in the nucleus and also expressed in the cytoplasm.1.There were significant differences in the expression of CDX2 protein in chronic gastritis group,intestinal metaplasia group and gastric cancer group?P<0.01?.The expression level of CDX2 protein in intestinal metaplasia group was significantly higher than that in chronic gastritis group and gastric cancer group?P<0.05?.The expression of CDX2 protein in gastric cancer tissues was significantly correlated with the age,lymph node metastasis and TNM stage?P<0.05?.The expression level of CDX2 was significantly higher in patients with stage I-II gastric cancer than that in patients with stage III-IV gastric cancer.It was significantly higher in patients without lymph node metastasis than in patients with lymph node metastasis.It was significantly higher in patients aged 65 years or older than those younger than 65 years old.2.There were significant differences in the expression of P1-HNF4?protein in chronic gastritis group,intestinal metaplasia group and gastric cancer group?P<0.01?.The expression level of P1-HNF4?protein in gastric cancer group was significantly higher than that in chronic gastritis group.The expression level of P1-HNF4?protein in intestinal metaplasia group was significantly higher than that in gastric cancer group?P<0.01?.The expression of P1-HNF4?protein in gastric cancer tissues was significantly correlated with T stage.The expression level of P1-HNF4?was significantly higher in patients with T1-2 stage gastric cancer than those with T3-4 stage gastric cancer?P<0.05?.3.The expression level of P2-HNF4?protein in chronic gastritis group was significantly lower than that in intestinal metaplasia group and gastric cancer group?P<0.01?,but there was no significant difference between intestinal metaplasia group and gastric cancer group?P>0.05?.The expression level of P2-HNF4?protein in gastric cancer tissues was significantly correlated with clinical TNM stage.The expression level of P2-HNF4?in patients with stage III+IV gastric cancer was significantly higher than those with stage I+II gastric cancer?P<0.05?.4.CDX2,P1-HNF4?and P2-HNF4?were positively correlated in chronic gastritis?r=0.361,0.338,0.392,P<0.05?.There was a significant positive correlation between CDX2,P1-HNF4?and P2-HNF4?in intestinal metaplasia?r=0.675,0.626,0.59,P<0.01?.There was a significant positive correlation between CDX2 and P1-HNF4?expression in gastric cancer tissues?r=0.604,P<0.01?.The expression of CDX2 and P2-HNF4?was positively correlated in gastric cancer?r=0.464,P<0.01?.There was a positive correlation between the expression of P1-HNF4?and P2-HNF4?in gastric cancer tissues?r=0.441,P<0.01?.5.Low expression of CDX2 and high expression of P2-HNF4?were associated with poor prognosis in patients with gastric cancer?P<0.05?.The prognosis of gastric cancer patients was analyzed by CDX2 and P2-HNF4?.The Kaplan-Meier survival curve showed that the survival rate of gastric cancer patients with CDX2^High/P2-HNF4?^Low group was the highest,and the CDX2^Low/P2-HNF4?^High group had the worst survival rate?P<0.05?.The expression of P1-HNF4?was not associated with the prognosis of patients with gastric cancer?P>0.05?.Conclusions:1.Both CDX2 and HNF4?are involved in the evolution of gastric intestinal metaplasia and gastric cancer,but their effects are different.2.The expression patterns of P1-HNF4?and CDX2 are similar,which may mainly regulate the differentiation of intestinal epithelial cells,and play an important role in the process of intestinal metaplasia of gastric mucosa.At the same time,both may exist as protective factors to inhibit the invasion and metastasis of gastric cancer.3.P2-HNF4?may promote tumorigenesis in gastric cancer.4.CDX2 and P2-HNF4?can be used as a biological indicator to evaluate the prognosis of patients with gastric cancer.