Associated Study About The Expression Of HIF-1α And INOS In The Gastric Cancer With Hp Infection

OBJECTIVE:To test Hp infection and the genotypes of gastric cancer patients andgastritis patients,and to study the expression of HIF-1α,iNOS and their relevance ingastric mucosa of patients with gastric cancer and gastritis with different genotypes,andto explore the role of HIF-1α,iNOS in the occurrence of gastric cancer,and to explorethe carcinogenic mechanisms of Hp.METHODS:(1)Hp was identified with rapid urease,Giemsa staining and ¹⁴C-breath testfor 212 patients with gastric cancer and 110 patients with gastritis.(2) The cagA andvacA genotypes of Hp were determined by PCR method for those patients that haveinfected Hp,including 138 patients with gastric cancer and 53 patients with gastritis.(3)The expression of HIF-1α,iNOS in the gastric mucosa of all patients were detected byimmunohistochemical method,and to analyze the relevance of the expression of HIF-1α,iNOS and HP infection and the different genotypes.RESULT:(1)198 patients were screened from 212 patients with gastric cancer,which138 cases were Hp-positive and 60 cases were Hp-negative,the positive rate was 69.7%;98 patients were screened from 110 patients with gastritis,which 53cases wereHp-positive and 45 cases were Hp-negative,the positive rate was 54.1%,the positive rateof HP infection for patients with gastric cancer was significantly higher than that forpatients with gastritis,there was a significant difference (P＜0.01).(2) 191 patients of Hp-positive contain vacA gene,which 138 cases were patients withgastric cancer and 53 cases were patients with gastritis,but not all carry cagA gene.95patients were cagA(+) and 43 patients were cagA (-) from Hp-positive 138 patients withgastric cancer,the positive rate was 68.8%,14 patients were cagA(+) and 39 patientswere cagA (-) from Hp-positive 53 patients with gastritis,the positive rate was 26.4%,Hp-positive patients with gastric cancer carrying cagA gene were more than Hp-positivepatients with gastritis carrying cagA gene,there was a significant difference (P＜0.01).(3) 149 patients were HIF-1α-positive and 49 patients were HIF-1α-negative from 198patients with gastric cancer,the positive rate was 75.3%,2 patients were HIF-1α-positiveand 96 patients were HIF-1α-negative from 98 patients with gastritis,the positive ratewas 2.0%,HIF-1α-positive rate of patients with gastric cancer was significantly higher than that of patients with gastritis,there was a significant difference (P＜0.01).113patients were HIF-1α-positive and 25 patients were HIF-1α-negative from 138 patients ofHp-positive with gastric cancer,the positive rate was 81.9%,2 patients wereHIF-1α-positive and 51 patients were HIF-1α-negative from 53 patients of Hp-positivewith gastritis,the positive rate was 3.8%,HIF-1α-positive rate of patients of Hp-positivewith gastric cancer was significantly higher than that of patients of Hp-positive withgastritis,there was a significant difference (P＜0.01).36 patients were HIF-1α-positiveand 24 patients were HIF-1α- negative from 60 patients of Hp-negative with gastriccancer,the positive rate was 60.0%,0 patients were HIF-1α-positive and 45 patients wereHIF-1α-negative from 45 patients of Hp-negative with gastritis,the positive rate was0.0%,HIF-1α-positive rate of patients of Hp-negative with gastric cancer wassignificantly higher than that of patients of Hp-negative with gastritis,there was asignificant difference (P＜0.01).HIF- 1α-positive rate (81.9%) of patients of Hp-positivewith gastric cancer was higher than that (60.0%) of patients of Hp-negative with gastriccancer,there was a significant difference (P＜0.01).HIF-1α-positive rate (3.8%) ofpatients of Hp-positive with gastritis was higher than that (0.0%) of patients ofHp-negative with gastritis,there was not a significant difference (P＞0.05).(4) 133 patients were iNOS-positive and 65 patients were iNOS- negative from 198patients with gastric cancer,the positive rate was 67.2%,27 patients were iNOS-positiveand 71 patients were iNOS-negative from 98 patients with gastritis,the positive rate was27.6%,iNOS -positive rate of patients with gastric cancer was significantly higher thanthat of patients with gastritis,there was a significant difference (P＜0.01).100 patientswere iNOS-positive and 38 patients were iNOS-negative from 138 patients ofHp-positive with gastric cancer,the positive rate was 72.5%,16 patients wereiNOS-positive and 37 patients were iNOS-negative from 53 patients of Hp-positive withgastritis,the positive rate was 30.2%,iNOS-positive rate of patients of Hp-positive withgastric cancer was significantly higher than that of patients of Hp-positive with gastritis,there was a significant difference (P＜0.01).33 patients were iNOS -positive and 27patients were iNOS-negative from 60 patients of Hp-negative with gastric cancer,thepositive rate was 55.0%,11 patients were iNOS-positive and 34 patients wereiNOS-negative from 45 patients of Hp-negative with gastritis,the positive rate was 24.4%,iNOS -positive rate of patients of Hp-negative with gastric cancer wassignificantly higher than that of patients of Hp-negative with gastritis,there was asignificant difference (P＜0.01).iNOS-positive rate (72.5%) of patients of Hp-positivewith gastric cancer was higher than that (55.0%) of patients of Hp-negative with gastriccancer,there was a significant difference (P＜0.05).iNOS-positive rate (30.2%) ofpatients of Hp-positive with gastritis was higher than that (24.4%) of patients ofHp-negative with gastritis,there was not a significant difference (P＞0.05).(5) 89 patients were HIF-1α-positive and 6 patients were HIF-1α- negative from 95patients of cagA(+)vacA(+) genotype in 138 patients of Hp-positive with gastric cancer,the positive rate was 93.7%,2 patients were HIF-1α-positive and 12 patients wereHIF-1α-negative from 14 patients of cagA(+)vacA(+) genotype in 53 patients ofHp-positive with gastritis,the positive rate was 14.3%,HIF-1α-positive rate of patientsof cagA(+)vacA(+) genotype with gastric cancer was significantly higher than that ofpatients with gastritis,there was a significant difference (P＜0.01).24 patiems wereHIF-1α-positive and 19 patients were HIF-1α- negative from 43 patients ofcagA(-)vacA(+) genotype with gastric cancer,the positive rate was 55.8%,0 patientswere HIF-1α-positive and 39 patients were HIF-1α- negative from 39 patients ofcagA(-)vacA(+) genotype with gastritis,the positive rate was 0.0%,HIF-1α-positive rateof patients of cagA(-)vacA(+) genotype with gastric cancer was significantly higher thanthat of patients with gastritis,there was a significant difference (P＜0.01).HIF-1α-positive rate(93.7%) of patients of cagA(+)vacA(+) genotype with gastric cancerwas significantly higher than that (55.8%)of cagA(-)vacA(+) genotype with gastriccancer,there was a significant difference (P＜0.01).HIF-1α-positive rate(14.3%) ofpatients of cagA(+)vacA(+) genotype with gastritis was significantly higher than that(0.0%) of cagA(-)vacA(+) genotype with gastritis,there was not a significant difference(P＞0.05).(6) 77 patients were iNOS-positive and 18 patients were iNOS-negative from 95 patientsof cagA(+)vacA(+) genotype in patients of Hp-positive with gastric cancer,the positiverate was 81.1%,7 patients were iNOS-positive and 7 patients were iNOS-negative from14 patients of cagA(+)vacA(+) genotype in patients of Hp-positive with gastritis,thepositive rate was 50%,iNOS-positive rate of patients of cagA(+)vacA(+) genotype with gastric cancer was significantly higher than that of patients with gastritis,there was asignificant difference (P＜0.01).23 patients were iNOS-positive and 20 patients wereiNOS-negative from 43 patients of cagA(-)vacA(+) genotype with gastric cancer,thepositive rate was 53.5%,9 patients were iNOS-positive and 30 patients wereiNOS-negative from 39 patients of cagA(-)vacA(+) genotype with gastritis,the positiverate was 23.1%,iNOS-positive rate of patients of cagA(-)vacA(+) genotype with gastriccancer was significantly higher than that of patients with gastritis,there was a significantdifference (P＜0.01).iNOS-positive rate(81.1%) of patients of cagA(+)vacA(+) genotypewith gastric cancer was significantly higher than that (53.5%)of cagA(-)vacA(+)genotype with gastric cancer,there was a significant difference (P＜0.01).iNOS-positiverate(50.0%) of patients of cagA(+)vacA(+) genotype with gastritis was significantlyhigher than that (23.1%) of cagA(-)vacA(+) genotype with gastritis,there was not asignificant difference (P＞0.05).(7) The correlation between HIF-1αand iNOS expression:in the gastric cancer group,totally 198 cases,149 cases were HIF-1α-positive,and 49 cases wereHIF- 1α-negative;133 cases were iNOS-positive,and 65 cases were iNOS-negative;109cases were both negative,25 cases were both negative.It showed that there was a positivecorrelation between HIF-1αand iNOS expression(r=0.57,P＜0.01).In the gastric cancergroup with cagA(+)vacA(+) gene type and Hp-positive,totally 95 cases,89 cases wereHIF-1α-positive and 6 cases were HIF-1α-negative;77 cases were iNOS-positive and 18cases were iNOS-negative;75 cases were both positive and 4 cases were both negative,Itshowed that there was a positive correlation between HIF-1αand iNOSexpression(r=0.698,p＜0.01) in the gastric cancer group with cagA(+)vacA(+)expression and Hp-positive.In the gastric cancer group with cagA(-)vacA(+) gene typeand Hp-positive,totally 43 cases,24 cases were HIF-1α-positive,and 19 cases wereHIF-1α-negative;23 cases were iNOS-positive and 20 cases were iNOS-negative;13cases were both positive and 9 cases were both negative.There was no correlationbetween HIF-1αand iNOS expression in the cagA(-)vacA(+)gene type gastric cancergroup(r=0.002,P＞0.05).HIF-1αdid not express in gastritis group,so we did not analysisthe correlation between them.CONCLUSION:Hp infection of people was associated with the occurrence of gastric cancer,and especially the cagA and vacA genotypes of Hp were closely associated withthe occurrence of gastric cancer.This study further confirmed that HIF-1αand iNOS playan important role in the formation of gastric cancer,and both of them were cooperatewith each other.