| Background:The incidence and mortality of Gastric Carcinoma(GC)in China ranks second and third respectively in malignant tumors,which seriously threatens the health of Chinese people.Gastric intestinal metaplasia(IM)is an important precancerous lesion that increases the risk of gastric cancer development.IM usually develops into gastric cancer after 10-20 years of followup,providing a wide time window for clinical intervention of gastric cancer,so it is considered to be a key stage in the prevention and control of gastric cancer.However,current studies have shown that eradication of Helicobacter pylori(Hp),reduction of inflammation and other treatments seem to be difficult to reverse IM,suggesting that there may be other maintenance factors in the occurrence of IM.Caudal type homeobox 2(CDX2)is a gut-specific transcription factor that plays an important role in the development,differentiation and phenotypic maintenance of the gut.Cell experiments and transgenic mouse studies have shown that CDX2 can directly promote the transcription of intestinalspecific genes and the occurrence of IM.Therefore,abnormal expression and activation of CDX2 is a key event in IM.Bile acids(BAs)are generally considered to be carcinogenic to human gastrointestinal cancer.Clinical and epidemiological studies have shown that bile reflux is an important risk factor for IM and gastric cancer.Farnesoid X receptor(FXR)and G protein-coupled receptor TGR5,which are the two most critical receptors for BAs,mediate the regulation of downstream signaling pathways and cellular functions by BAs.We have previously demonstrated that FXR is involved in bile acid-induced expression of CDX2 and its downstream molecules.So,understanding the expression and clinical significance of FXR,TGR5 and CDX2 in chronic gastritis,IM and gastric cancer tissues will provide a reference for further study of the key mechanisms of bile acid involved in the development of IM and gastric cancer.Part 1 Expression and Significance of TGR5 and CDX2 in Gastric Intestinal Metaplasia and Gastric Carcinoma Objective:To investigate the expression and significance of TGR5 and CDX2 in the gastric intestinal metaplasia and gastric carcinoma.Methods:Immunohistochemical staining was used to detect the expression of TGR5 and CDX2 in 50 cases of chronic gastritis,86 cases of IM and 98 cases of gastric cancer.The differences in expression of TGR5 and CDX2 between the groups were compared,and the relationship between the expression of TGR5 and CDX2 and the clinicpathological parameters and prognosis of gastric cancer patients were analyzed.Spearman rank correlation test was used to analyze the correlation between the TGR5 and CDX2 expression.Results:The high expression rates of TGR5 in the IM and gastric cancer tissues were 53.5% and 58.2%,respectively(P>0.05),but they were significantly higher than chronic gastritis tissues(18.0%)(P<0.001).High expression of TGR5 was associated with TNM stage(III+IV stage)(P=0.004),lymph node metastasis(P=0.046),and worse prognosis(P=0.006)of patients with gastric cancer.The high expression rate of CDX2 in the gastric cancer tissues(30.6%)was significantly lower than that in IM tissues(48.8%)(P<0.05),but both were significantly higher than those in the chronic gastritis tissues(2.0%)(P<0.001).High expression of CDX2 was associated with the TNM stage(I+II stage)(P=0.008),no lymph node metastasis(P=0.014),and better prognosis(P=0.023)in patients with gastric cancer.There was no correlation between TGR5 and CDX2 expression in the chronic gastritis and IM(P>0.05),but they were positively correlated in the gastric cancer(P=0.003).Conclusions:TGR5 and CDX2 are significantly up-regulated in both IM and gastric cancer tissues,and may be involved in the occurrence and development of IM and gastric cancer.Part 2 Expression and Significance of FXR and CDX2 in Gastric Intestinal Metaplasia and Gastric Carcinoma Objective:To investigate the expression and clinical significance of FXR and CDX2 in gastric intestinal metaplasia and gastric cancer.Methods:Immunohistochemical staining was used to detect the expression of FXR and CDX2 in 30 cases of chronic gastritis,50 cases of IM and 60 cases of gastric cancer.The chi-square test was used to compare the expression differences of FXR and CDX2 in each group,and the relationship between the expression of FXR and CDX2 and the clinicopathological parameters of intestinal metaplasia and gastric cancer patients was analyzed.Spearman rank correlation test was used to analyze the correlation between the FXR and CDX2 expression.Results:The high expression rates of FXR in IM and gastric cancer tissues were 58.0% and 38.3%,respectively,which were significantly higher than those in chronic gastritis(13.3%)(P<0.05).Compared with IM tissues,FXR expression was significantly decreased in gastric cancer tissues(P=0.040).FXR expression is related to the degree of IM.Compared with mild IM tissues(41.7%),FXR expression was significantly increased in moderate to severe IM tissues(73.1%)(P=0.025).FXR expression is related to the differentiation status of gastric cancer.Compared with moderate or well differentiated gastric cancer tissues(65.0%),FXR expression was significantly decreased in poor differentiated gastric cancer tissues(25.0%)(P=0.003).The high expression rates of CDX2 in IM and gastric cancer tissues were 46.0% and 26.7%,respectively,which were significantly higher than those in chronic gastritis(6.7%)(P<0.05).Compared with IM tissues,CDX2 expression was significantly decreased in gastric cancer tissues(P=0.035).CDX2 expression is related to the degree of IM.Compared with mild IM tissue(25.0%),CDX2 expression was significantly increased in moderate to severe IM tissues(65.4%)(P=0.004).CDX2 expression is related to the differentiation status of gastric cancer.Compared with moderate or well differentiated gastric cancer tissues(60.0%),CDX2 expression was significantly decreased in poor differentiated gastric cancer tissues(10.0%)(P<0.001).There was a significant positive correlation between FXR and CDX2 expression in chronic gastritis,IM,and gastric cancer tissues(P<0.001).Conclusion:FXR and CDX2 are up-regulated in IM and gastric cancer tissues and have a significant positive correlation.They may be involved in the occurrence and development of IM and gastric cancer. |
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