scholarly journals Precancerous Gastric Lesions with Helicobacter pylori vacA+/babA2+/oipA+ Genotype Increase the Risk of Gastric Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Theeraya Simawaranon Bartpho ◽  
Wareeporn Wattanawongdon ◽  
Taweesak Tongtawee ◽  
Chatchanok Paoin ◽  
Kokiet Kangwantas ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Clinical Outcomes ◽  
Chronic Gastritis ◽  
Virulence Genes ◽  
Gastric Lesions ◽  
Precancerous Gastric Lesions ◽  
Increased Risk ◽  
H Pylori ◽  
Gastric Cancer Patients

Objective. The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods. Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori infection and virulence genes (cagA, vacA, iceA2, babA2, and oipA) were determined using real-time PCR. The association between H. pylori genotypes and clinical outcomes were evaluated using multivariate regression model analysis. The overall survival of gastric cancer patients was compared between genotype combinations. Results. H. pylori was positive in 166 patients with chronic gastritis, precancerous gastric lesions, and gastric cancer. The genes vacA, babA2, and oipA were most prevalent in chronic gastritis (73%), precancerous gastric lesions (62%), and gastric cancer (91%), respectively. The vacA, babA2, and oipA genes were associated with increased risk of gastric cancer (OR = 1.23; 95% CI = 1.13–3.32; P=0.033, OR = 2.64; 95% CI = 1.44–4.82, P=0.024, and OR = 2.79; 95% CI = 1.58–5.41; P=0.031, respectively). Interestingly, H. pylori vacA+/babA2+/oipA+ genotype infection was associated with increased risk of gastric cancer (OR = 3.85, 95% CI = 1.67–5.77, P=0.014). Conclusion. In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.

scholarly journals Expression of Cancer Stem Cell Marker CD44 and Its Polymorphisms in Patients with Chronic Gastritis, Precancerous Gastric Lesion, and Gastric Cancer: A Cross-Sectional Multicenter Study in Thailand

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Taweesak Tongtawee ◽  
Wareeporn Wattanawongdon ◽  
Theeraya Simawaranon ◽  
Soraya Kaewpitoon ◽  
Sivamate Kaengpenkae ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Cancer Patients ◽  
Chronic Gastritis ◽  
Stem Cell Marker ◽  
Gastric Lesions ◽  
Cd44 Expression ◽  
Precancerous Gastric Lesions ◽  
Significant Difference ◽  
Gastric Cancer Patients

Here we investigated CD44 protein expression and its polymorphisms in patients with chronic gastritis, precancerous gastric lesions, and gastric cancer; and we evaluated our result with the risk of CD44 protein expression and clinicopathological characteristics. Our results obtained by analyzing 162 gastric cancer patients, 125 chronic gastritis, and 165 precancerous gastric lesions from three study centers in Thailand showed that CD44 expression was significantly higher in patients with precancerous gastric lesions and gastric cancer while patients with chronic gastritis were negative for CD44 staining (p=0.036). We further observed the significant association of variant genotype; gastric cancer patients carrying AG or GG of CD44 rs187116 had more increased risk of CD44 expression than wild-type (WT) carriers (AG: odds ratio (OR) = 5.67; 95% CI = 1.57–7.23; p=0.024 and GG: OR = 8.32; 95% CI = 2.94–11.42; p=0.016), but no significant difference in the risk of CD44 expression due to polymorphism in patients with precancerous gastric lesions. Our results suggested that CD44 expression could be used as a marker for the prediction of gastric cancer development, particularly in patients with precancerous gastric lesions carrying AG or GG, who were selected to surveillance follow-up for gastric cancer prevention.

scholarly journals Transcriptional Profile of Helicobacter pylori Virulence Genes in Patients with Gastritis and Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Manouchehr Ahmadi Hedayati ◽  
Saeed Salavati
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Carcinoma ◽  
Clinical Outcomes ◽  
Virulence Genes ◽  
Gastric Biopsy ◽  
Transcriptional Profile ◽  
Statistical Correlations ◽  
H Pylori ◽  
Antral Biopsy

Introduction. Numerous molecular epidemiology studies have been performed about the frequency of Helicobacter pylori virulence genes in patients with H. pylori infection so far. This study was conducted to detect transcriptional profile by cDNA of H. pylori virulence genes in gastric biopsy samples of gastritis and gastric carcinoma patients. Materials and Methods. In a case-control study, based on the prevalence of gastritis and gastric cancer in Sanandaj city during 2018 and 2019, 23 and 11 gastric antral biopsy samples with H. pylori infection were collected from gastritis and gastric carcinoma patients by the consecutive and available sampling method. Pathological characters, including tumor grades and tumor areas for gastric carcinoma biopsy samples prepared from gastric cancer areas, were determined by the pathologist. Total RNA of gastric antral biopsy samples was extracted, and their cDNA was synthesized by TaKaRa kit. H. pylori virulence genes’ cDNA using specific primers and PCR was detected. This study’s results were analyzed by SPSS version 25 and statics chi-square tests for determination of relationship and correlation between cDNAs of H. pylori transcriptional profile and clinical outcomes of H. pylori infection, including gastritis, gastric carcinoma, tumor grades, and tumor area. Results. The positive statistical correlations were observed between transcripts of cagA, cagA-EPIYAC, cagE, and cagY genes and H. pylori infection clinical outcomes ( P < 0.05 ). Conclusion. Detection of the H. pylori virulence genes’ cDNA in gastric biopsy samples can help provide the prognosis of clinical outcomes.

scholarly journals Infection with Helicobacter Pylori Presenting the vacA s2m2 haplotype is Strongly Associated with Protection Against Gastric Cancer

2021 ◽  
Author(s):  
Alix Guevara-Tique ◽  
Fabian Castro Valencia ◽  
John Jairo Suaréz Olaya ◽  
Roberto Carlos Torres ◽  
Giovanna Parra ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Virulence Genes ◽  
Mortality Rates ◽  
South American ◽  
Gastric Lesions ◽  
Preneoplastic Lesions ◽  
Main Risk Factor ◽  
South American Region ◽  
H Pylori

Abstract Background: Infection with Helicobacter pylori is recognized as the main risk factor for gastric cancer (GC); the clinical outcome of this infection is variable and partially depends on the virulence of the infective strain. This study characterizes H. pylori virulence genes in patients with diverse gastric lesions, from preneoplasia to GC, from a South American region with high GC mortality rates.Methods: We studied the virulence profiles of H. pylori strains to colonize the antrum of 318 patients with non-atrophic gastritis (NAG), 58 patients with preneoplastic lesions (PN), and 90 with GC from Ibagué, Colombia. The presence of 16S rDNA, the cagA and cagE genes, and the vacA s1, s2, m1, and m2 alleles were determined by PCR.Results: H. pylori infection was detected in 44% of all patients, 41.2% in NAG, 43.1% in PN and 54.4% of GC patients (p= 0.0813). cagA and cagE genes were significantly more frequent in and GC than in NAG (p= <.0001). The vacA s1m1 haplotype was significantly more frequent in PN (68%) and GC (65.3%) than in NAG (37.4%). The frequency of vacA s2m2 haplotype decreased significantly from NAG (42.7%) to PN (12%) and this to GC (4.1%). A total of 23 different genotypes were identified, with cagA+/cagE+/vacA s1m1 (84/205) as the more frequent in PN and GC and cagA-/cagE-/vacA s2m2 in NAG (49/205).Conclusions: In the population studied, vacA s2m2 was identified as a significant marker for protection against PN and GC, and genotype cagA+/cagE+/vacA s1m1 as a marker for increased GC risk. We also found that patients with PN and GC had a higher frequency of cagA+/cagE+/vacA s1m1 H. pylori strains known to be aggressive.

scholarly journals Helicobacter pyloriAnti-CagA Antibodies: Prevalence in Symptomatic and Asymptomatic Subjects in Turkey

2002 ◽  
Vol 16 (8) ◽  
pp. 527-532 ◽  
Author(s):  
M Fatih Abasiyanik ◽  
Ersan Sander ◽  
Barik A Salih
Keyword(s):  
Gastric Cancer ◽  
Duodenal Ulcer ◽  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Chronic Gastritis ◽  
Molecular Weights ◽  
Cancer Antigens ◽  
Gastroduodenal Disease ◽  
H Pylori ◽  
Asymptomatic Subjects

BACKGROUND: Several reports have shown the prevalence of anti-CagA antibodies to be associated with the development of peptic ulcer diseases, while others have indicated that there is no such association.AIM: To examine the prevalence of antibodies to CagA and otherHelicobacter pyloriantigens in symptomatic and asymptomatic subjects in Turkey.SUBJECTS AND METHODS: Sixty-six symptomatic subjects, 16 to 74 years of age, were examined forH pyloriby biopsy-based tests and ELISA. One hundred nineteen asymptomatic subjects, 20 to 65 years of age, were also tested serologically for the presence ofH pylori. Samples from both groups that were found to be positive forH pyloriby ELISA were then tested by immunoblotting.RESULTS: Fifty-four (82%) symptomatic subjects and 76 (64%) asymptomatic subjects were found to beH pylori-positive by ELISA. Samples from 30 symptomatic subjects who were found to beH pylori-positive by ELISA were analyzed by immunoblotting. Antibodies to CagA (116 kDa) antigen were detected in immunoblots of 11 of 14 (79%) with chronic gastritis, 12 of 13 (92%) with duodenal ulcer and three of three (100%) with gastric cancer. Antigens of the following molecular weights were also detected in these 30 subjects: 89 kDa (VacA) in 21 (70%), 37 kDa in 21 (70%), 35 kDa in 19 (63%), 30 kDa in 27 (90%) and 19.5 kDa in 19 (63%). Immunoblots of 40 ELISA-positive asymptomatic subjects showed that 33 (83%) had antibodies to CagA antigen, 26 (65%) to VacA antigen, 30 (75%) to a 37 kDa antigen, 30 (75%) to a 35 kDa antigen, 39 (98%) to a 30 kDa antigen and 36 (90%) to a 19.5 kDa antigen.CONCLUSIONS: Antibodies to CagA antigen were prevalent in both groups, regardless of the presence of gastroduodenal disease.

scholarly journals Induction and prevention of gastric cancer with combined Helicobacter pylori and capsaicin administration and DFMO treatment, respectively

2020 ◽  
Author(s):  
Faisal Aziz ◽  
Mingxia Xin ◽  
Yunfeng Gao ◽  
Josh Monts ◽  
Kjersten Monson ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Mouse Models ◽  
Chronic Gastritis ◽  
Molecular Mechanisms ◽  
Gastric Carcinogenesis ◽  
Lifestyle Changes ◽  
Host Susceptibility ◽  
Anti Inflammatory ◽  
H Pylori

Abstract Background: Gastric cancer risk evolves over time due to environmental, dietary, and lifestyle changes including Helicobacter pylori (H. pylori) infection and consumption of hot peppers (i.e. capsaicin). H. pylori infection promotes gastric mucosal injury in the early phase of capsaicin exposure. In addition, capsaicin consumption is reported to suppress immune function and increase host susceptibility to microbial infection. This relationship suggests a need to investigate the mechanism of how both H. pylori infection and capsaicin contribute to gastric inflammation and lead to gastric cancer. No previous experimental animal models have been developed to study this dual association. Here we developed a series of mouse models that progress from chronic gastritis to gastric cancer. C57-Balb/c mice were infected with the H. pylori (SS1) strain and then fed capsaicin (0.05% or 0.2g/kg/day) or not. Consequently, we investigated the association between H. pylori infection and capsaicin consumption during the initiation of gastric inflammation and the later development of gastric cancer. Tumor size and phenotype were analyzed to determine the molecular mechanism driving the shift from gastritis to stomach cancer. Gastric carcinogenesis was also prevented in these models using the ornithine decarboxylase inhibitor DFMO (2-difluoromethylornithine). Results: This study provides evidence showing that a combination of H. pylori infection and capsaicin consumption leads to gastric carcinogenesis. The transition from chronic gastritis to gastric cancer is mediated through interleukin-6 (IL-6) stimulation with an incidence rate of 50%. However, this progression can be prevented by treating with anti-inflammatory agents. In particular, we used DFMO to prevent gastric tumorigenesis by reducing inflammation and promoting recovery of disease-free stasis. The anti-inflammatory role of DFMO highlights the injurious effect of inflammation in gastric cancer development and the need to reduce gastric inflammation for cancer prevention. Conclusions: Overall, these mouse models provide reliable systems for analyzing the molecular mechanisms and synergistic effects of H. pylori and capsaicin on human cancer etiology. Accordingly, preventive measures like reduced capsaicin consumption, H. pylori clearance, and DFMO treatment can lessen gastric cancer incidence. Lastly, anti-inflammatory agents like DFMO can play important roles in prevention of inflammation-associated gastric cancer.

scholarly journals Genetic Polymorphisms of CXCL8 (−251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients

2019 ◽  
Author(s):  
Wongwarut Boonyanugomol ◽  
Kamolchanok Rukseree ◽  
Worrarat Kongkasame ◽  
Prasit Palittapongarnpim ◽  
Seung-Chul Baik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Gene Polymorphisms ◽  
Inflammatory Responses ◽  
Increased Risk ◽  
Cxc Chemokine ◽  
H Pylori

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection and gastric cancer among Thai gastroduodenal patients, gene polymorphisms in CXCL8 (promoter region -251) and in CXCR1 and CXCR2 (receptors for CXCL8) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR (AS-PCR). We also determined the presence of cytotoxin-associated gene A (cagA) in Thai patients with H. pylori infection. Correlation between the CXCL8 (-251) polymorphism and CXCL8 gene expression was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). We found a significant association between the T/A and A/A genotypes of CXCL8 (-251) with H. pylori infection. However, no significant correlation was found between the CXCR1 (+2607) and CXCR2 (+1208) gene polymorphisms with H. pylori infection among Thai gastroduodenal subjects. Within the H. pylori-infected group of Thai gastroduodenal patients, no significant differences in cagA were observed. In addition, the A/A genotype of CXCL8 (-251) significantly correlated with the risk of gastric cancer and correlated with higher CXCL8 gene expression levels in Thai gastroduodenal patients. These results suggest that CXCL8 (-251) polymorphisms are associated with H. pylori infection, an increased risk of stronger inflammatory responses, and gastric cancer in Thai gastroduodenal patients.  

scholarly journals Western-Type Helicobacter pylori CagA are the Most Frequent Type in Mongolian Patients

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 725 ◽  
Author(s):  
Tegshee Tserentogtokh ◽  
Boldbaatar Gantuya ◽  
Phawinee Subsomwong ◽  
Khasag Oyuntsetseg ◽  
Dashdorj Bolor ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Patients ◽  
East Asian ◽  
Virulent Strains ◽  
Virulent Type ◽  
High Incidence ◽  
Caga Status ◽  
H Pylori ◽  
Gastric Cancer Patients

Helicobacter pylori infection possessing East-Asian-type CagA is associated with carcinogenesis. Mongolia has the highest mortality rate from gastric cancer. Therefore, we evaluated the CagA status in the Mongolian population. High risk and gastric cancer patients were determined using endoscopy and histological examination. H. pylori strains were isolated from different locations in Mongolia. The CagA subtypes (East-Asian-type or Western-type, based on sequencing of Glu-Pro-Ile-Tyr-Ala (EPIYA) segments) and vacA genotypes (s and m regions) were determined using PCR-based sequencing and PCR, respectively. In total, 368 patients were examined (341 gastritis, 10 peptic ulcer, and 17 gastric cancer). Sixty-two (16.8%) strains were cagA-negative and 306 (83.1%) were cagA-positive (293 Western-type, 12 East-Asian-type, and one hybrid type). All cagA-negative strains were isolated from gastritis patients. In the gastritis group, 78.6% (268/341) had Western-type CagA, 2.9% (10/341) had East-Asian-type, and 18.2% (61/341) were cagA-negative. However, all H. pylori from gastric cancer patients possessed Western-type CagA. Histological analyses showed that East-Asian-type CagA was the most virulent strains, followed by Western-type and cagA-negative strains. This finding agreed with the current consensus. CagA-positive strains were the most virulent type. However, the fact that different CagA types can explain the high incidence of gastric cancer might be inapplicable in Mongolia.

scholarly journals Gastric Microbiota in Helicobacter pylori-Negative and -Positive Gastritis Among High Incidence of Gastric Cancer Area

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 504 ◽  
Author(s):  
Boldbaatar Gantuya ◽  
Hashem B. El-Serag ◽  
Takashi Matsumoto ◽  
Nadim J. Ajami ◽  
Khasag Oyuntsetseg ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Bacterial Species ◽  
Rrna Gene ◽  
Linear Discriminant ◽  
Haemophilus Parainfluenzae ◽  
Increased Risk ◽  
Comparison Groups ◽  
H Pylori ◽  
Gastric Microbiota

Helicobacter pylori (H. pylori) related chronic gastritis is a well-known major etiological factor for gastric cancer development. However, H. pylori-negative gastritis (HpN) is not well described. We aimed to examine gastric mucosal microbiota in HpN compared to H. pylori-positive gastritis (HpP) and H. pylori-negative non-gastritis group (control). Here, we studied 11 subjects with HpN, 40 with HpP and 24 controls. We performed endoscopy with six gastric biopsies. Comparison groups were defined based on strict histological criteria for the disease and H. pylori diagnosis. We used 16S rRNA gene amplicon sequencing to profile the gastric microbiota according to comparison groups. These results demonstrate that the HpP group had significantly lower bacterial richness by the operational taxonomic unit (OTU) counts, and Shannon and Simpson indices as compared to HpN or controls. The linear discriminant analysis effect size analysis showed the enrichment of Firmicutes, Fusobacteria, Bacteroidetes and Actinobacteria at phylum level in the HpN group. In the age-adjusted multivariate analysis, Streptococcus sp. and Haemophilus parainfluenzae were at a significantly increased risk for HpN (odds ratio 18.9 and 12.3, respectively) based on abundance. Treponema sp. was uniquely found in HpN based on occurrence. In this paper, we conclude that Streptococcus sp., Haemophilus parainfluenzae and Treponema sp. are candidate pathogenic bacterial species for HpN. These results if confirmed may have important clinical implications.

bghcng.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15521-e15521
Author(s):  
Carlos Castaneda Altamirano ◽  
Carolina Belmar Lopez ◽  
Miluska Castillo Garcia ◽  
Jais Nieves ◽  
Julio Polo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Risk Factor ◽  
Cancer Patients ◽  
Detection Rate ◽  
Virulence Genes ◽  
Virulence Gene ◽  
Gastric Cancer Patients ◽  
Tumoral Area ◽  
Common Infections

e15521 Background: Helicobacter pylori (HP) infection is one of the most common infections worldwide and is a risk factor for gastric cancer (GC) development. This study was conducted to determinate the prevalence rate of HP as well as presence of vacA and cagA in gastric cancer samples from Peruvian patients. Methods: GC samples were prospectively collected from patients who went to surgery between April 2015 and November 2016. Three types of gastric samples were obtained from each patient: tumoral area (T), proximal healthy (P) and distal healthy tissue (D) samples. HP status through H&E was analyzed by a pathologist. DNA was extracted from tissue, and detection of colonization (ureA and hspA) and virulence genes (vacA and cagA) of HP was performed through quantitative PCR (qPCR). Results: A total of 183 patients were studied with a mean age of 64 years and 51.9% were men. 52.2% had a primary from antrum, 47.8% was HG 3 and 60% were diffuse. Presence of HP through H&E was found in 58.4% (n=107/183). Positive HP cases through qPCR were determinate with positivity of at least one ureA/hspA gene and was found in 89.6% (n=164/183). HP detection rate and its concentration were higher in D (ureA: 62.8%, n=115, [703.58±245.47pg]; hspA: 73.8%, n=135, [42.77±10.17pg]) than P (ureA: 59.0%, n=108, [539.69±121.32pg]; hspA: 71.0%, n=130, [31.90±8.64pg]) and T (ureA: 49.7%, n=91, [296.32±164.98pg]; hspA: 70.5%, n=129, [4.6±1.33pg]) (p<.001). Antrum location was associated to higher level of hspA expression (p=0.047). Neither histology (p=0.45) nor HG (p=0.2) was associated to level of hspA expression. qPCR detected HP in 75% (n=57/76) of cases without evidence of HP by pathology evaluation (H&E) (ICC: 0.77 vs 0.58). cagA virulence gene was detected in 95.8% (n=159/166) while vacAm allele in 85.5% (n=142/166) and vacAs allele in 96.8% (n=160/166). vacA+cagA- combination was found in 0.6% (n=1/166), vacA+cagA+ cases in 95.8% (n=159/166) and vacA-cagA- cases in 3.6% (n=3/166). Conclusions: Our results show a significant presence of HP in Peruvian gastric cancer patients and combination of vacA+/-cagA+/- virulence genes had particular patterns.

scholarly journals Functional Analysis of the cag Pathogenicity Island in Helicobacter pylori Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer

2004 ◽  
Vol 72 (2) ◽  
pp. 1043-1056 ◽  
Author(s):  
Steffen Backert ◽  
Tobias Schwarz ◽  
Stephan Miehlke ◽  
Christian Kirsch ◽  
Christian Sommer ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Pathogenicity Island ◽  
Epidemiological Studies ◽  
Disease Development ◽  
Gastric Diseases ◽  
H Pylori ◽  
Gastric Cancer Patients

ABSTRACT Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.

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