Relationship between Helicobacter pylori virulence genes and gastroduodenal disease.

OBJECTIVE: This study aimed to identify Helicobacter pylori virulence factors and examine their associations with clinical outcomes in Thai patients. Moreover, the association between these genotypes and gastric mucosa morphological patterns was investigated. METHODS: This retrospective study enrolled patients who underwent esophagogastroduodenoscopy at Suranaree University of Technology Hospital. The presence of the cagA and vacA genes was investigated by real-time polymerase chain reaction. RESULTS: The H. pylori-specific genes ureA and 16S rRNA were detected in all 698 gastric biopsy specimens. In total, 567 (81.23%) patients with H. pylori infection were positive for the cagA gene, 443 (63.46%) were positive for the vacA gene, and 370 (53.0%) were positive for both. The cagA genotype was significantly more common in patients with chronic gastritis and peptic ulcers (78.99% and 79.41%, respectively) than the vacA gene (51.48% and 55.88%, respectively) and combined genotypes (32.34% and 47.05%, respectively). Moreover, the cagA genotype was significantly more common in patients with type 4 or 5 gastric mucosa patterns (69.49% and 76.31%, respectively). CONCLUSIONS: The cagA genotype is the main cause of serious inflammation of the gastric mucosa. The cagA gene is possibly an important factor explaining gastroduodenal disease outcomes in Thai patients with H. pylori infection.

Expression of Matrix Metalloproteinase-7 Predicts Poor Prognosis in Gastric Cancer.

To date, no potential markers have been established for predicting prognosis in gastric cancer. Matrix metalloproteinase-7 (MMP-7) has been suggested as a prognostic marker in several cancers. In this study, we aimed to determine the expression of the MMP-7 protein and its polymorphisms in gastric cancer tissues. The association between MMP-7 expression level and clinicopathological characteristics was also evaluated. MMP-7 protein expression and its polymorphisms were investigated in a total of 400 patients using immunohistochemistry and TaqMan SNP genotyping assays. The correlation of MMP-7 expression with clinicopathological characteristics, including tumor location, tumor size, histologic type, lymphatic invasion, vascular invasion, pathological T stage, pathological TNM stage, residual tumor, and CEA level, was investigated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a multivariate Cox proportional hazards regression model. MMP-7 expression was found in 283 of 400 (70.75%) gastric cancer tissues. Expression of MMP-7 was significantly associated with poor clinicopathological characteristics, including vascular invasion (OR = 6.61, 95%CI = 4.26-9.89, p = 0.024), lymphatic invasion (OR = 8.17, 95%CI = 4.47-12.39, p = 0.017), undifferentiated histologic type (OR = 2.46; 95% CI, 1.31-4.52; p = 0.014), higher TNM stage (stage IV) (OR = 1.48, 95%CI = 1.08-3.08, p = 0.047), and high CEA level (OR = 5.96, 95%CI = 2.12-8.12, p = 0.026). We further observed a significant association of the variant genotype; gastric cancer patients carrying GG of MMP-7 (-181A/G; rs11568818) had a greater increased risk of MMP-7 expression than did 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). These findings suggest that MMP-7 expression can be used to predict the prognosis of gastric cancer patients.

The mouse double minute 2 polymorphism is associated with both decreased p53 expression and poor clinicopathological outcomes of gastric cancer.

This study aimed to determine the mouse double minute 2 (MDM2) SNP309 polymorphism and to evaluate MDM2 and p53 expression and the association of MDM2 positivity in gastric cancer and clinicopathological outcomes. A total of 400 patients with chronic gastritis, precancerous lesions, and gastric cancer were used to identify the MDM2 SNP309 polymorphism by using the Taq Man SNP Genotyping assay. Immunohistochemistry was performed to evaluate MDM2 and p53 expression. The associations of polymorphisms, protein expression, clinicopathological outcomes, and gastric cancer risk were calculated by multivariate Cox proportional hazards regression model analysis and expressed by odds ratios (ORs) and 95% confidence intervals (CIs). The MDM2 SNP309 G/G homozygous polymorphism was significantly associated with expressed MDM2 in gastric cancer (OR = 1.57, 95% CI = 1.39-2.03, P = 0.039). Moreover, in gastric cancer, p53 was significantly decreased compared to MDM2 (P = 0.007). However, MDM2 and p53 expression were not significantly different among genotypes, and the G/G genotype can result in the altered protein expression of p53 in gastric cancer. Clinicopathological outcome was significantly associated with MDM2 expression, including tumor location in the upper gastric region (OR = 1.48, 95% CI = 1.25-3.54, P = 0.037), undifferentiated type (OR = 2.47, 95% CI = 1.38-4.14, P = 0.016), presence of lymphatic invasion (OR = 1.96, 95% CI = 1.22-3.19, P = 0.014), and unresectable tumor (OR = 3.39, 95% CI = 1.61-4.94, P = 0.017). Our study indicated associations of the MDM2 SNP309 G/G homozygous polymorphism, MDM2 and p53 expression. Therefore, G/G-associated MDM2 revealed that P53 expression was decreased in gastric cancer and poor clinicopathological outcomes. Understanding the genetic polymorphisms and expression of MDM2 may help explain gastric cancer risk.

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

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), 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. H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of. RESULTS: H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of vacA, babA2, and oipA genes and their association with clinical outcomes. vacA, babA2, and oipA genes and their association with clinical outcomes. P=0.033, OR = 2.64; 95% CI = 1.44-4.82, P=0.033, OR = 2.64; 95% CI = 1.44-4.82, P=0.033, OR = 2.64; 95% CI = 1.44-4.82, H. pylori vacA +/babA2, and oipA genes and their association with clinical outcomes. P=0.033, OR = 2.64; 95% CI = 1.44-4.82. 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.H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of H. pylori vacA +/babA2, and oipA genes and their association with clinical outcomes.

Expression of CD44 and MDM2 in cholangiocarcinoma is correlated with poor clinicopathologic characteristics.

The aim of the study was to investigate the expression of cluster of differentiation 44 (CD44) and mouse double minute 2 (MDM2) in cholangiocarcinoma, in addition to evaluating their association with clinicopathologic characteristics and overall survival time. Paraffin-embedded tumor tissues from 128 patients from 3 study centers in Thailand were evaluated using immunohistochemistry. The results demonstrated that positive expression of CD44 was associated with high histologic grade (P=0.013), large tumor size (P=0.027), lymph node metastasis (P=0.037), and distant metastasis (P=0.031). MDM2 expression was related to high histologic grade (P=0.013), lymph node metastasis (P=0.025), and distant metastasis (P=0.016). Furthermore, multivariate analyses revealed that combined expression of CD44 and MDM2 was significantly associated with worse overall survival time (OR=1.52; 95% CI=1.04-2.26; P=0.041) in patients with cholangiocarcinoma. CD44 and MDM2 significantly indicate poor clinicopathologic outcomes in patients with cholangiocarcinoma.

Genetic polymorphisms in TLR1, TLR2, TLR4, and TLR10 of Helicobacter pylori-associated gastritis: a prospective cross-sectional study in Thailand.

The toll-like receptors (TLRs) mediate the recognition of Helicobacter pylori and initiate the innate immune response to infection. We hypothesized those genetic polymorphisms in the TLR1, TLR2, TLR4, and TLR10 influence bacterial infection, affecting susceptibility H. pylori to disease outcomes. Genomic DNA was extracted and genotypes of TLR1 (rs4833095), TLR2 (rs3804099 and rs3804100), TLR4 (rs10759932), and TLR10 (rs10004195) polymorphism were detected by the TagMan single-nucleotide epolymorphisms genotyping assay using the real-time PCR hybridization probe method. The TLR1 (rs4833095), C allele and the TLR10 (rs10004195), A allele frequency was significantly increased risk in the H. pylori infection group (odds ratio=1.76, 95% confidence interval=1.84-2.15, P=0.01 and odds ratio=1.81, 95% confidence interval=1.18-3.26, P=0.04, respectively). The TLR1 (rs4833095), C allele and TLR10 (rs10004195), A allele are susceptible TLRs polymorphisms in the Thai population. These findings suggest that TLR1 rs4833095 and TLR10 rs10004195 may play crucial roles in H. pylori susceptibility and gastric pathogenesis.

Role of toll-like receptor 10 gene polymorphism and gastric mucosal pattern in patients with chronic gastritis.

BACKGROUND/AIMS: Helicobacter pylori stimulates the host's toll-like receptors (TLRs). Single-nucleotide polymorphism (SNP) of TLRs is related to the manipulation of regulatory cytokines and also implicated in the varied outcomes of the inflammatory response, including the development of precancerous lesions of gastric mucosa and disease progression. We hypothesized that TLR10 rs10004195 polymorphism is associated with gastric mucosal patterns. MATERIALS AND METHODS: TLR10 rs10004195 polymorphisms were identified in a total of 400 gastritis patients using the TagMan SNP genotyping assay. Gastric mucosal patterns were classified by Conventional Narrow Band Imaging gastroscopy (C-NBI gastroscopy). Logistic regression was used to analyze the association. RESULTS: The gastritis patients was Type 1, 37.5% of Thai patients. The T/T homozygous genotype was exhibited by the highest percentage (46.5%) of patients, and the A/A homozygous and A/T heterozygous genotypes were exhibited by 20.25% and 33.25%, respectively, of patients. TLR10 rs10004195 was significantly associated with gastric mucosal patterns. After adjusting for confounding factors, patients with the A/A homozygous genotype showed a significantly increased risk of severe inflammation (OR=1.35, 95% CI=0.97-2.13, p=0.028). Patients with the A/T heterozygous and T/T homozygous genotypes showed a significantly increased risk of mild inflammation (OR=1.24, 95% CI=0.78-2.07, p=0.042 and OR=1.78, 95% CI=0.51-3.35, p=0.001, respectively). CONCLUSION: Our results indicate that the presence of TLR10 rs10004195, A/T heterozygous, and T/T homozygous genotypes is associated with type 1, 2, and 3 whereas that of the A/A homozygous genotype is associated with type 4 and 5 of gastric mucosal patterns. This suggests that the A/A homozygous genotype contributes to severe inflammation in H. pylori-associated gastritis in Thai patients.

TLR1 Polymorphism Associations with Gastric Mucosa Morphologic Patterns on Magnifying NBI Endoscopy: a Prospective CrossSectional Study.

BACKGROUND: Helicobacter pylori is now recognized as a causative factor of chronic gastritis, gastroduodenal ulcers, gastric cancer and mucosaassociated lymphatic tissue lymphoma. Tolllike receptors are important bacterial receptors in gastric epithelial cell signaling transduction and play critical roles in gastric carcinogenesis. MATERIALS AND METHODS: A total of 400 patients undergoing esophagogastroduodenoscopy for investigation of chronic abdominal pain were genotyped for singlenucleotide polymorphisms (SNPs) in TLR1 (rs4833095) using TagMan SNPs genotyping assay by realtime PCR hybridization. Relationships with susceptibility to H. pylori infection and premalignant gastric mucosa morphological patterns, classified by magnifying NBI endoscopy, were investigated. RESULTS: The percentages of TLR1 rs4833095, CC homozygous, CT heterozygous and TT homozygous cases were 34, 46.5 and 19%, respectively. CC showed statistical differences between H. pylori positive and negative cases (P<0.001). CT and TT correlated with type 1 and type 2 gastric mucosal morphological patterns (P<0.01) whereas CC correlated with types 3 and 4 (P<0.01). CONCLUSIONS: This study demonstrated good correlation of TLR1 rs4833095 genotype with severity of inflammation in H. pylori infected gastric mucosa according to gastric mucosal morphologic patterns with magnifying NBI endoscopy.

Improved Detection of Helicobacter pylori Infection and Premalignant Gastric Mucosa Using Conventional White Light Source Gastroscopy.

BACKGROUND: The gold standard diagnosis of H. pylori related gastritis is evidence of bacteria on histopathological examination of gastric mucosa. Our aim was to study the correlation between gastric mucosal morphology and histopathological severity of H. pylori related gastritis. MATERIALS AND METHODS: Division was made on morphological features into:Type 1, showing regular arrangement of red dots; Type 2, showing cleft-like appearance; Type 3, with a mosaic appearance; and Type 4, having a mosaic appearance with focal or diffuse hyperemia. RESULTS: Types 1 and 2 gastric mucosal morphologies were statistically significant in predicting an H. pylori negative status (137/145, <0.01), while Types 3 and 4 were significant a positive status (139/155, <0.01). The sensitivity, specificity, positive and negative predictive values of Type 3 and 4 morphologies for predicting H. pylori positive were 94.6%, 89.5%, 89.7% and 94.5%, respectively, with a good correlation with inflammation grading (<0.01). CONCLUSIONS: Our study suggests that gastric mucosal morphology can be reliably identified using conventional white light source gastroscopy with good correlation between findings and inflammation grading.