Identificating H.pylori Dominant Genotypes In Gastric Intestinal Metaplasia Of Paracarcinoma And Relationship With P-STAT3 And CDX2 Expression

ObjectiveTo screen the H.pylori dominant genotypes of gastric intestinal metaplasia(GIM)by detecting the distribution of H.pylori vac A and cagA subtypes in gastric cancer(GC),GIM and no GIM tissue(control).To discuss the carcinogenesis mechanism of GC and GIM by analysis the relationship between H.pylori dominant genotypes and STAT3,p-STAT3 and CDX2 expression in GC,GIM and control group,so that H.pylori could be eradicated according to the genotypes and gastric cancer could be controlled in the pre-cancerous lesion stage.MethodsTotal 163 cases of H.pylori positive paraffin-embedded gastric cancer and adjacent tissues were collected from the Department of Pathology,Affiliated First Hospital of China Medical College from 2011 to 2014,including 140 cases of moderate to poor differentiation GC,23 cases well differentiation GC,93 cases intestinal type GC,and 70 cases diffuse type GC.There were 106 cases of GIM,including 7 cases ? type GIM,40 cases ? type GIM and 59 cases ? type GIM,and 57 cases no-intestinal metaplasia as control.Using the DNA Extraction Kit to extract DNA from paraffin-embedded tissues;Using PCR and methylene blue staining to judging the positive of H.pylori;Using PCR and nested PCR to distinguish the subtypes of vacA and cagA gene;Using HID-AB-PAS staining to distinguish the subtypes of GIM;Using the immunohistochemistry method to detect the expression of STAT3,p-STAT3,CDX2 in GC and GIM.The differences between groups were tested using ?2 or Fisher's exact test using SPSS 23.0.A P-value of less than 0.05 was considered statistically significant.ResultsThe distribution of H.pylori dominant genotypes in control,GIM and GC.The composition of vacAsl genotype in control group was significantly higher than other subtypes in the same group,while the composition of cagA+,vacAml and vacAslml genotypes in control group were significantly lower than other subtypes in the same group(P<0.05).In GIM group,the composition rate of cagA+,vacAs1,vacAml,vacAs1m1,genotypes were higher than other subtypes in the same group(P<0.05).The composition of cagA+,vacAsl,vacAm1,vacAslml genotypes in GC group were significantly higher than other subtypes in the same group(P<0.05).The composition of cagA+ and vacAs1m1 genotypes in GIM and GC groups were higher than control group,which the differences were statistically significant.The relationship between the dominant genotypes of H.pylori and the differentiation of GC and Lauren classification.In cagA+ and vacAslml genotypes group,the ratio of moderately and poorly differentiated GC were significantly higher than the well differentiation GC group(P<0.05).The differences were statistically significant compared with other subtypes in the same group.In cagA+,vacAs1m1 genotype groups,the ratio of diffuse type GC were significantly higher than intestinal type GC in the same group,and there were significant statistical differences.The distribution of H.pylori dominant gene subtypes in different subtypes of GIM.In cagA+ and vacAs1m1 genotypes group the ratio of subtype ? was higher than subtype I and II,respectively.Comparing with subtype ? and ? in the same group,there were significant statistical differences.The relationship between the dominant genotypes of H.pylori and STAT3 expression.In cagA+ genotype group,the positive rate of STAT3 in GIM and GC groups was higher than other genotypes in the same groups(P<0.05)while the positive rate of STAT3 in GIM was significantly higher than control and GC groups(P<0.05).In vacAslml genotype group,the positive rate of STAT3 in control,GIM and GC groups was higher than other genotypes in the same groups(P<0.05);the positive rate of STAT3 in GIM was significantly higher than that in GC groups(P<0.05).The relationship between the dominant genotypes of H.pylori and p-STAT3 expression.In cagA+ genotype group,the positive rate of p-STAT3 in control group was lower than other genotypes in the same group(P<0.05),while the positive rate of p-STAT3 in GIM and GC groups was higher than other genotypes in the same groups(P<0.05);the positive rate of p-STAT3 in control group was significantly higher than that in GIM and GC groups(P<0.05).The relationship between the dominant genotypes of H.pylori and the expression of CDX2.In cagA+ and vacAs1m1 genotype group,the positive rate of CDX2 in GIM and GC groups was lower than other genotypes in the same group(P<0.05);In cagA+ and vacAslml genotype group the positive rate of CDX2 in control group was significantly lower than that in GIM and GC groups(P<0.05).Conclusions1.H.pylori cagA+ and vacAslml dominant genotypes have close relatationship with GC,which were closely related with moderate/poor differentiated GC and diffuse type GC.2.H.pylori cagA+ and vacAs1m1 dominant genotypes have close relatationship with GIM,which were closely related to subtype ? GIM.3.In GC and GIM,cagA+ and vacAs1m1 H.pylori genotypes have a positive relationship with p-STAT3 expression,negative relationship with CDX2 expression.4.GIM infected by vacAs1m1 and cagA+ genotypes H.pylori,especially subtye ?,accompanied by positive expression p-STAT3,negative expression of CDX2 was more closely related to GC.These kind GIM should be eradicated H.pylori and followed up regularly.