cagA In Patients Research Articles

Gastric Tumor Suppressor Genes Alterations Associated with cag A Positive H pylori among Patients with Gastric Cancer Systemic Review and Meta-Analysis

Introduction: Gastric cancer is the fifth most frequent cancer worldwide After lung, breast, colorectal, and prostate cancers. Helicobacter pylori (H. pylori) is considered the most important causative agent of gastrointestinal diseases such as peptic ulcer, gastritis, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. Objective: to identify the tumor suppressor genes alterations associated with CagA in patients with gastric cancer. Methods: All the available papers published before 2022 were collected by searching in PubMed and Scopus. The keywords included in the research were “H.pylori”, “gastric cancer”, “virulence factors”, “tumor suppressor genes” “ gene mutations” “cagA+” used by Boolean operators to obtain the articles with the keywords in their titles or abstracts. Result: Initial searches yielded 111 articles, four articles were excluded as a duplication using the computer program Zotero (v5), then one hundred and seven articles were screened for the title and abstract evaluation using the Rayyan website, among them seventy-one articles were excluded. Thirty-six articles were scanned for full-text review and eligibility, furthermore, twenty-five articles were excluded because there were either Reviews and case reports, Not relevant studies, Insufficient data, and Unclear methods and results. Eleven articles were included for the literature review. In addition, the studies were in different regions of the world including Asia, Europe, North America, and Latin America. However, most of the studies were related to the USA. Conclusion: Cag A can cause alterations on gastric tumor suppressor genes by either decreased expression by increasing the methylation, inducing point mutation as mentioned, inactivation by increasing the methylation levels, increasing the levels of degradation and methylation the promotor of the tumor suppressor gene as mentioned.

Genetic differences between Helicobacter pylori strains isolated from patients with chronic mild and severe gastritis

Background. Helicobacter pylori-associated chronic gastritis (CG), being a very heterogeneous group, still does not have a divisin based on Helicobacter pylori (Hp) genotyping data, which could predict the clinical form of CG.The aim of the study is to search for the prevalence of the cagA gene or any allelic combination of the vacA gene, or stable combinations of cagA and any allelic combination of vacA genes in Hp isolates from patients with mild and severe CG, as well as patients with peptic ulcer disease (PUD).Methods. Hp isolates from gastrobiopsy specimens were genotyped for cagA and vacA allelic combinations (s1m1, s2m1, s1m2, s2m2). The difference in the occurrence of vacA allelic combinations was assessed by Mann–Whitney U test; the conjunction of cagA and vacA allelic combinations was assessed by the Spearman's rank correlation coefficient (rs).Results. The cagA gene was found in more than half of all cases, both in patients with ulcer and in patients with CG (mild and severe). The incidence of vacAs1m1 (the most virulent allelic combination) showed no significant differences in all forms of gastritis and in PUD; the correlation between cagA and vacAs1m1 was significant in all groups of patients, rs ranged from 0.57 to 0.72. In patients with mild CG, an abundance of non-virulent allelic combination vacAs2m2 was observed, which was significantly different from its occurrence both in patients with severe CG and in patients with ulcer; the joint occurrence of vacAs2m2 and cagA in patients with mild CG was chaotic (rs=-0.13; P=0.40).Conclusion. In mild CG, despite the absence of significant differences in cagA and vacAs1m1 (when compared with severe CG and ulcer disease), strains with a non-virulent allelic combination vacAs2m2 were significantly dominant; therefore, the detection of this particular allelic combination of vacA speaks in favor of a mild course of CG.

Elevated Levels of Interferon-γ Are Associated with High Levels of Epstein-Barr Virus Reactivation in Patients with the Intestinal Type of Gastric Cancer.

Background The inflammatory response directed against Helicobacter pylori (HP) is believed to be one of the main triggers of the appearance of gastric lesions and their progression to gastric cancer (GC). Epstein-Barr virus (EBV) has been found responsible for about 10% of all GCs, but the inflammatory response has not been studied in GC patients with evidence of high levels of EBV reactivation. Objective To determine the relationship between inflammation and antibodies against EBV reactivation antigens, HP, and the bacterium virulence factor CagA in patients with GC. Methods 127 GC patients, 46 gastritis patients, and 197 healthy subjects were studied. IL-1β, IL-6, IL-8, IL-10, TNF-α, TGF-β, MCP-1, and IFN-γ levels were measured in serum or plasma and compared against the antibody titers of VCA-IgG, HP, and the HP virulence factor CagA. Statistical associations were estimated. Results Significant ORs and positive trends were found between VCA-IgG and IFN-γ, specifically for patients with GC of intestinal type (OR: 6.4, 95% C.I. 1.2–35.4) (p < 0.044). Conclusions We confirmed a positive association between a marker of EBV reactivation and intestinal gastric cancer and present evidence of a correlation with elevated serum levels of IFN-γ, but not with the other cytokines.

The relationship of Cag-A in patients with HP positive alopecia areata and vitiligo

The relationship of Cag-A in patients with HP positive alopecia areata and vitiligo

Different Gastric Mucosa and CagA Status of Patients in India and Japan Infected with Helicobacter pylori

Despite similar incidence of Helicobacter pylori infection, the frequency of gastric cancer is sevenfold higher in Japan than in India. The objective of this work was to define differences in H. pylori-induced gastritis and to identify the bacterial virulence factors involved. We prospectively enrolled 353 consecutive patients who underwent endoscopy and received three gastric biopsies in Tokyo, Japan, and Hyderabad, India. Immunohistochemistry against H. pylori and East Asian CagA and hematoxylin-eosin and Giemsa stain were used to examine gastric mucosal biopsy specimens. Histological scores were assessed in accordance with the updated Sydney System. Subjects with H. pylori infection were matched by age and sex to compare histopathology and bacterial virulence. Sixty patients infected with H. pylori were prospectively selected. Median histological scores for neutrophil and mononuclear cell infiltration and for atrophy were significantly higher in Japan than in India (neutrophils 4.0 vs 3.0, p < 0.01; mononuclear cells 5.0 vs 4.5, p = 0.03; atrophy 3.0 vs 2.0, p < 0.01, respectively). Scores for H. pylori density and intestinal metaplasia were also higher in Japan, albeit without statistical significance (H. pylori 5.0 vs 3.0, p = 0.08; intestinal metaplasia 0.0 vs 0.0, p = 0.08). Prevalence of East Asian CagA-positive H. pylori was significantly higher in Japan (73.3 vs 0.0 %, p < 0.01). The significantly higher prevalence of histologically severe gastritis and East Asian CagA in patients from Japan with H. pylori infection may be involved in the pathogenesis of gastric cancer.

Serum concentrations of Helicobacter pylori IgG and the virulence factor CagA in patients with ischaemic heart disease

To compare the serum concentrations of IgG to Helicobacter pylori and its virulence factor CagA in patients with ischaemic heart disease (IHD), we recruited 120 patients with IHD [acute myocardial infarction (AMI) (n = 60); unstable angina (UA) (n = 60)] and 60 sex- and age-matched healthy controls in this study. The seroprevalence of anti-H. pylori IgG was 86.7% in AMI, 91.7% in UA patients and 58.3% in the control group with mean titres of 33.2 U/ml [standard error (SE) 4.76], 57.96 U/ml (SE 7.54) and 25.72 U/ml (SE 4.01) respectively. The seroprevalence of anti-H. pylori in the patient groups was significantly higher than the control group. The mean levels of anti-H. pylori in the AMI and UA groups were also significantly higher than in the control group. The seroprevalence and mean titre of anti-CagA IgG did not differ significantly between patient and control groups.

Age and Severity of Mucosal Lesions Influence the Performance of Serologic Markers in Helicobacter pylori–Associated Gastroduodenal Pathologies

The course of Helicobacter pylori infection and antibody response to CagA in patients with preneoplastic lesions and gastric cancer has not been thoroughly studied. We aimed to study H. pylori infection and antibody response to CagA in patients with non-atrophic gastritis, preneoplastic lesions, and gastric cancer. We studied patients attending one Oncology Hospital and one General Hospital in Mexico City. Diagnosis was based on endoscopy and histopathology in biopsies from six stomach regions. H. pylori infection was assessed by histology and serology, and antibodies against CagA were measured with immunoassay. We included 618 patients, 368 with non-atrophic gastritis, 126 with precancerous lesions, and 65 with gastric cancer; in addition, 59 patients with duodenal ulcer were studied. Detection of infection and IgG against CagA had a significant increase from non-atrophic gastritis to mild and up to advanced stages of metaplasia (P < 0.05), followed by decreased infection and IgG to CagA in patients with gastric cancer (P < 0.05). However, infection and CagA antibodies were associated with young gastric cancer cases. Duodenal ulcer showed a significant association with infection detected by histology and serology, particularly among women, and a trend to associate with IgG to CagA. This study shows that H. pylori infection and CagA are risk markers for intestinal metaplasia. The prevalence of these risk markers decreases in gastric cancer, probably reflecting that infection decreases after advanced atrophy and metaplasia in the gastric mucosa. State of the disease, age, and sex influence the association of H. pylori infection and IgG response to CagA with gastroduodenal diseases.

Serum positive cagA in patients with non-ulcer dyspepsia and peptic ulcer disease from two centers in different regions of Turkey.

To investigate and compare frequencies of serum positive cagA in patients from two separate regions of Turkey who were grouped according to the presence of peptic ulcer disease or non-ulcer dyspepsia. One hundred and eighty Helicobacter pylori-positive patients with peptic ulcer disease or non-ulcer dyspepsia were included in the study. One hundred and fourteen patients had non-ulcer dyspepsia and 66 had peptic ulcer disease (32 with gastric ulcers and/or erosions and 34 with duodenal ulcers). Each patient was tested for serum antibody to H. pylori cagA protein by enzyme immunoassay. The total frequency of serum positive cagA in the study group was 97.2 %. The rates in the patients with peptic ulcers and in those with non-ulcer dyspepsia were 100 % and 95.6 %, respectively. These results were similar to those reported in Asian studies, but higher than those that have been noted in other studies from Turkey and Western countries. The high rates of serum positive cagA in these patients with peptic ulcer disease and non-ulcer dyspepsia were similar to results reported in Asia. The fact that there was high seroum prevalence regardless of ulcer status suggests that factors other than cagA might be responsible for ulceration or other types of severe pathology in H. pylori-positive individuals.

Accuracy of a commercial enzyme-linked immunosorbent assay for CagA in patients from Brazil with and without gastric carcinoma.

We validated a commercial enzyme-linked immunosorbent assay for the detection of anti-CagA antibodies in Brazilian patients with Helicobacter pylori infection. The test presented high sensitivity (97.4%) and specificity (88.9%) when employed in patients without gastric carcinoma. However, in gastric carcinoma patients, the test was neither sensitive nor specific enough to detect cagA-positive H. pylori infection.

Phosphorylation of Helicobacter pylori CagA in patients with gastric ulcer and gastritis.

The effects of Helicobacter pylori infection are strongly associated with chronic gastritis, gastric and duodenal ulcer, gastric cancer, and MALT lymphoma. The microorganism has been classified as a type I carcinogen by the World Health Organization. Varying clinical results from H. pylori infection are believed due, in part, to differences in virulence among species. The cag pathogenicity island is a complex of virulent genes and a coding region for the type IV phosphorylated secretion system. Through this system, many virulent gene products or proteins are phosphorylated into the host cells. This study demonstrated the positive CagA-phosphorylation effect of H. pylori in patients with chronic gastritis and benign gastric ulcer and revealed significantly different rates of CagA phosphorylation between these two diseases (P<.05).

Seropositivity against Helicobacter pylori CagA in Turkish gastric cancer patients.

Increased prevalence of CagA in gastric cancer has been reported; yet, other reports suggest that the cagA gene is not associated with gastric cancer. To evaluate the frequency of CagA seropositivity in Turkish patients with gastric cancer. Thirty-two patients with gastric adenocarcinoma and 46 patients with nonulcer dyspepsia were examined for Helicobacter pylori status and for antibodies against CagA. H. pylori was positive in 56.3% of patients and in 71.7% of controls. CagA was positive in all patients in the study group, regardless of H. pylori positivity, and in 56.5% of the control group. CagA positivity in H. pylori -positive patients was significantly more frequent in patients with gastric cancer than in those with nonulcer dyspepsia ( p < 0.001). As for H. pylori -negative patients in both groups, CagA positivity was also more frequent in gastric cancer patients ( p < 0.001). Testing for H. pylori antibodies without testing for antibodies against CagA will miss patients with either recent or previous infection, which may be a cause of missing the relationship between H. pylori and gastric cancer. The authors think that testing for CagA in patients with dyspepsia can reveal which patients should be followed up for the risk of developing gastric cancer.