Abstract
OBJECTIVE To analyze positive rates of the specific proteins CagA, VacA, UreA and UreB of Helicobacter pylori (Hp) in people in Xinin city Qinghai Province, a district with a high prevalence of gastric carcinoma, and to examine the relationship among the incidence, gross diagnosis and pathologic diagnosis.
METHODS The gastric tissue biopsy specimens taken under endoscopy were examined by CLO, WS and Western Blot to judge the condition of the Hp infection. The positive rates of Hp CagA, VacA, UreA and UreB that had infected patients were evaluated.
RESULTS The positive rate of UreA was markedly lower in chronic superficial gastritis (CSG) than in duodenal ulcer (DU) and compound ulcer, and also lower than in chronic atrophic gastritis(CAG), gastric ulcer(GU) and gastric cancinoma. However the positive rate of UreB was notably lower in duodenal ulcer and gastric ulcer than in chronic superficial gastritis and atrophic gastritis. The rates of UreB found in intestinal epithelial metaplasia, atrophic gastritis and gastric carcinoma were notably lower than in other diseases, however, it was markedly increased in chronic superficial gastritis. No differences were found among CagA and VacA of specimens with different endoscopic diagnosis or pathologic diagnosis.
CONCLUSIONS The UreA in Hp may be relevant to the pathogenic mechanism of severe gastric diseases. However, UreB may have some protective effect on severe gastric diseases.
keywords
Qinghai Province is one of the districts in China with a high incidence of gastric carcinoma, with the highest adjusted mortality of 40.62/100,000 [1]. But Helicobacter pylori (Hp) is the most important cancer-inducing factor for the human being stated by the World Health Organization International Agency for Research on Cancer(IARC)[2]. It was reported that different types of Hp could lead to different clinical results [3]. Therefore, further studies on the relationship between the specific proteins of Hp and gastric carcinoma were conducted.
MATERIALS AND METHODS
Research subjects
The 190 subjects of this investigation were examined by endoscopy in Qinhai Province People’s Hospital from January 1, 2000 to October 1, 2001. There were 135 males and, 55 females, the ratio of male to female being 2.45:1; ages ranged from 20 to 82 years, averaging 49.2. The ethinc background of the patients was as follows: Han ethnic group 139(73.2%), Hui ethnic group 30 (15.8%), Zang ethnic group 13 (6.8%), and the other minority ethnic groups 8 (4.2%). The patients clinical conditions: gastric carcinoma 86 (45.3%), peptic ulcer 38(20.0%), gastritis 66(34.7%); other data concerning the patients: a group of generations living in the district 127 (66.8%); a group of contemporary or previous generations immigrating into the district 63 (33.2%); peasants 63 (33.1%), workers 37 (19.4%), government works 43 (22.6%), and the other professionals 29 (15.3%), and those being out of work 18(9.5%).
Experimental method
Two pieces of tissue specimen taken at endoscopy from the gastric antrum and corpus were examined by the fast urea enzyme test (CLO) with Kits purchased from Haikou Nanke Science and Technology Development Company Limited. Another two pieces of tissue were examined by argyrophilic staining(WS dye) and pathologic inspection. Two ml of venous blood was conserved in a –70°C freezer for a serum immune blot test. The reagent kits were purchased from BLOT Company in Shenzhen, China. The infection rate was judged positive when both the CLO test and WS dye test were positive in comparison to the result of the serum immune blot test.
RESULTS
The total number of patients infected with Hp was 161, the infection rate being 84.7%. Those with gastric carcinoma were 86 (45.3%) in the 190 cases. Of the 161 with positive Hp, 147 were selected for analysis with a statistical method (using SPSS8.0 statistical software), because their data were more comprehensive than the others. The positive numbers were as follows: CagA, 124, the rate being 84.4% ; VacA, 124, the rate being 84.4%; UreA, 75, the rate being 51.0%; UreB, 76, the rate being 51.7%. The positive rates of UreA and UreB were similar.
The relation between the expression of VacA, CagA, UreA, UreB and the diagnoses by endoscopy
The positive rates of CagA and VacA were not notably different in all kind of diseases, P>0.05; the positive rate of UreA and UreB was notably different compared with the diseases considered, P<0.05. The results shown in Table 1.
The relation between the expression of CagA, VacA, UreA, UreB and the diagnosis by endoscopy
The positive rate of UreA was notably lower in chronic superficial gastritis than in duodenal ulcer and compound ulcer, also lower than in chronic atrophic gastritis, gastric ulcer and gastric carcinoma, but the positive rate of UreB was notably lower in duodenal ulcer and gastric ulcer than in chronic superficial gastritis and atrophic gastritis. This indicated that UreA may induce gastric ulcer, but UreB may have a protective effect for duodenal ulcer and gastric ulcer.
The relation between the positive expression of CagA, VacA, UreA, UreB and pathologic diagonoses
The expression of CagA and VacA showed no notable differences in chronic superficial gastritis, atrophic gastritis, intestinal epithelial metaplasia, mild atypical proliferation, moderate or severe atypical proliferation and gastric carcinoma, P>0.05. But UreA and UreB showed notable differences, P<0.05.UreA was notably lowered in chronic superficial gastritis. UreB was markedly lowered in intestinal epithelial metaplasia, chronic atrophic gastritis and gastric carcinoma, but significantly raised in chronic superficial gastritis, as shown in Table 2.
The relation between the expression of CagA, VacA, UreA, UreB and pathologic diagnosis (case, percentage)
DISCUSSION
The results of this research showed that the four kinds of antigens of CagA, VacA, UreA, UreB were all gastric disease–causing factors. Hp increased the risk of gastric carcinoma by promoting the development and change from gastric mucosa to precancerous lesions[1–3]. Some have presented the course through which chronic gastritis develops to become an intestinal type of gastric carcinoma asxhronic superficial gastritis→chronic atrophic gastritis→intestinal epithelial metaplas→atypical proliferation→gastric carcinoma, considering that atrophy and intestinal metaplasia were the primary stages of gastric carcinoma. Inflammation of the gastric mucosa could be aggravated, intestinal metaplasia and atrophy would be furthered by continuous infection with Hp, therefore, treatment to remove Hp could not only ameliorate the inflammation of gastric mucosa but also prevent the developmental course of intestinal epithelial metaplasia[4–7].
The positive rate of CagA, VacA, UreA and UreB in the serum of the group of patients infected with Hp was84.4, 84.4, 51.0 and 51.7 percent, respectively. It was found that there was no relationship between endoscopic or pathologic diagnosis and the positive rates of CagA or VacA, but there was a relationship with those of UreA and UreB in the population studied. Hp UreA may be correlated with severe gastric diseases such as peptic ulcer or gastric carcinoma. However, UreB may have a protective effect on gastric diseases. The results in this study and the results of the study reported by Yangweihong are unanimous [5]. It is suggested that there might be some relationship between the high expression of the UreA protein (relative molecular weight 30KD) and the intestinal epithelial metaplasia of the gastric mucosa of Hp-infected patients. The district is a region with high incidence of gastric carcinoma, and the Hp infection rate in the adult group is extremely high. Therefore, it is considered that Hp infection is essential in the development of gastric carcinoma in the district.
Researches [5,9] suggests that there is an association between the high expression of VacA protein (relative molecular weight 89KD) and the atrophy of gastric mucosa of Hp-infected patients. Zhangli et al[8] suggested an intimate relationship between the positive rate of Hp CagA and gastric carcinoma. But in our research we found no notable relation between the positive rates of CagA, VacA and endoscopic or pathologic diagonoses in Qinghai. Further studies are needed to explain the reason for these findings.
- Received February 19, 2004.
- Accepted April 10, 2004.
- Copyright © 2004 by Tianjin Medical University Cancer Institute & Hospital and Springer