Chronic Gastritis Group Research Articles

The metabolites mainly composed of lipids in tongue coating are non-invasive potential biomarkers for chronic gastritis

The changes in tongue coating metabolites in patients with chronic gastritis (CG) under different gastroscopy indicators were analyzed, and these metabolites were screened for potential non-invasive biomarkers to assist in the diagnosis of chronic gastritis. The technology of gas chromatography and liquid chromatography combined with mass spectrometry has been used to more comprehensively detect tongue coating metabolites of 350 CG patients. Spearman correlation analysis and random forest algorithm were used to screen metabolites that can serve as potential biomarkers. Compared with healthy individuals, CG group showed significant changes in the content of 101 metabolites, with an increase in the content of 54 metabolites and a decrease in the content of 47 metabolites. These differential metabolites are mainly composed of 47 lipids and lipid like substances. 1 metabolite was associated with bile reflux, 1 metabolite was associated with gastric mucosal erosion, 10 metabolites were associated with atrophy, 10 metabolites were associated with intestinal metaplasia, and 3 metabolites were associated with Helicobacter pylori infection. The ROC model composed of 5 metabolites can distinguish between CG group and healthy individuals, with an accuracy of 95.4%. The ROC model composed of 5,6-Dihydroxyindole can distinguish between chronic superficial gastritis group and chronic atrophic gastritis group, with an accuracy of 75.3%. The lipids and lipid like metabolites were the main abnormal metabolites in patients with chronic gastritis. It was worth noting that the content of Sphinganine 1-phase, 4-Ipomenol, and Nervonic acid in tongue coating increased, and the content of 1-Methyladenosine and 3-Hydroxycapric acid decreased, which helped to identify CG patients. The decrease in the content of 5,6-dihydroxyindole reminded patients that the development trend of CG was shifting from superficial to atrophic or even intestinal metaplasia. The detection of these metabolic markers of tongue coating was expected to be developed as a non-invasive and convenient technology in the future to assist us in monitoring and diagnosing the occurrence and development of CG.

Detection of CDH1 gene promoter hypermethylation in gastric cancer and chronic gastritis

AimThe current study aimed to assess the frequency of CDH1 promoter gene hypermethylation in gastric cancer and chronic gastritis and its correlation with clinicopathological aspects. MethodsMethylation-specific PCR was used to detect CDH1 promoter gene hypermethylation in 53 chronic gastritis patients and 40 gastric cancer patients along with normal adjacent tissues. ResultsThe chronic gastritis group comprised 29 males and 24 females with a mean age of 51.8 ± 12.96 years, and 49.1 % of them were positive for H. pylori infection. The frequency of CDH1 hypermethylation in gastritis lesions was 18.8 %. CDH1 hypermethylation showed a significant correlation with H. pylori infection (p = 0.039), but no significant association was observed with other clinical features. The gastric cancer group consisted of individuals with a mean age of 65.4 ± 10.6, among them, 77.5 % were male and 22.5 % were female, 62.5 % had PT3 tumors, 40 % had PN1 lymph node involvement, and the majority (47.5 %) of samples were obtained from body segment. CDH1 hypermethylation was significantly associated with depth of invasion (p = 0.017) and nodal invasion (p = 0.041) in this group. In both groups, normal adjacent specimens lacked CDH1 hypermethylation, and there was no statistically significant correlation between CDH1 hypermethylation and age at which the tumor was diagnosed, gender, activity level, or tumor location. ConclusionThis study demonstrates that E-cadherin methylation is associated with some characteristics of chronic gastritis and gastric cancer. These findings support previous research indicating that CDH1 hypermethylation may play a significant role in the development of gastric cancer.

Microbiome signatures associated with clinical stages of gastric Cancer: whole metagenome shotgun sequencing study

BackgroundGastric cancer is one of the global health concerns. A series of studies on the stomach have confirmed the role of the microbiome in shaping gastrointestinal diseases. Delineation of microbiome signatures to distinguish chronic gastritis from gastric cancer will provide a non-invasive preventative and treatment strategy. In this study, we performed whole metagenome shotgun sequencing of fecal samples to enhance the detection of rare bacterial species and increase genome sequence coverage. Additionally, we employed multiple bioinformatics approaches to investigate the potential targets of the microbiome as an indicator of differentiating gastric cancer from chronic gastritis.ResultsA total of 65 patients were enrolled, comprising 33 individuals with chronic gastritis and 32 with gastric cancer. Within each group, the chronic gastritis group was sub-grouped into intestinal metaplasia (n = 15) and non-intestinal metaplasia (n = 18); the gastric cancer group, early stage (stages 1 and 2, n = 13) and late stage (stages 3 and 4, n = 19) cancer. No significant differences in alpha and beta diversities were detected among the patient groups. However, in a two-group univariate comparison, higher Fusobacteria abundance was identified in phylum; Fusobacteria presented higher abundance in gastric cancer (LDA scored 4.27, q = 0.041 in LEfSe). Age and sex-adjusted MaAsLin and Random Forest variable of importance (VIMP) analysis in species provided meaningful features; Bacteria_caccae was the most contributing species toward gastric cancer and late-stage cancer (beta:2.43, se:0.891, p:0.008, VIMP score:2.543). In contrast, Bifidobacterium_longum significantly contributed to chronic gastritis (beta:-1.8, se:0.699, p:0.009, VIMP score:1.988). Age, sex, and BMI-adjusted MasAsLin on metabolic pathway analysis showed that GLCMANNANAUT-PWY degradation was higher in gastric cancer and one of the contributing species was Fusobacterium_varium.ConclusionMicrobiomes belonging to the pathogenic phylum Fusobacteria and species Bacteroides_caccae and Streptococcus_anginosus can be significant targets for monitoring the progression of gastric cancer. Whereas Bifidobacterium_longum and Lachnospiraceae_bacterium_5_1_63FAA might be protection biomarkers against gastric cancer.

Exploration of lncRNA/circRNA-miRNA-mRNA network in patients with chronic atrophic gastritis in Tibetan plateau areas based on DNBSEQ-G99 RNA sequencing

A higher incidence of chronic atrophic gastritis (CAG) is generally considered as a precancerous lesion in gastric cancer (GC). The aim of this study was to identify potential molecules involved in the pathogenesis of CAG in the Tibetan plateau, hoping to help the diagnosis and management of the disease. Atrophic and non-atrophic gastric mucosal tissue samples were collected from seven patients with chronic gastritis (CG). Differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs between CAG and chronic non-atrophic gastritis (CNAG) groups were identified based on DNBSEQ-G99 RNA sequencing. Subsequently, competitive endogenous RNA (ceRNA) regulatory networks (lncRNA/circRNA-miRNA-mRNA networks) were constructed. Two datasets (GSE153224 and GSE163416), involving data from non-Tibetan plateau areas, were used to further screen out Tibetan plateau key mRNAs, followed by the common genes of Tibetan plateau key and ferroptosis-related mRNAs were also identified. Functional enrichment analyses were performed to investigate the biological functions of Tibetan plateau mRNAs in the CAG. A total of seven lncRNA-miRNA-mRNA relationship pairs and 424 circRNA-miRNA-mRNA relationship pairs were identified in this study. The relationship pairs of hsa_circ_0082984-hsa-miR-204-5p-CACNG8, lncRNA DRAIC/has_circ_0008561-hsa-miR-34a-5p-AR/GXYLT2, lncRNA GAS1RR/RGMB-AS1/hsa_circ_0008561-hsa-miR-3614-5p-TMEM216/SUSD5, and LINC00941/hsa_circ_0082984-hsa-miR-873-3p-TMC5 can be involved in the pathogenesis of CAG. Additionally, eight common genes of Tibetan plateau key and ferroptosis-related differentially expressed mRNAs (DEmRNAs) (CBS, SLC2A4, STAT3, ALOX15B, ATF3, IDO1, NOX4, and SOCS1) were identified in CAG. The common genes of Tibetan plateau key and ferroptosis-related DEmRNAs can play a role in the JAK-STAT signaling pathway. This study identified important molecular biomarkers that may be involved in regulating the pathological mechanisms of CAG in the Tibetan plateau, which provides potential research directions for future research.

Pro-Inflammatory Diet as a Risk Factor for Stomach Cancer: Findings from a Multicenter Study in Central and Western China.

We conducted a multicenter cross-sectional study in central and western China to explore the association between inflammatory diet and stomach cancer odds. Participants from five hospitals in the central and western regions were collected. All participants completed the questionnaire we provided before the gastroscopy examination, which includes inquiries about risk factors for stomach cancer and food frequency. All participants underwent gastroscopy, and a mucosal biopsy was confirmed pathologically. Pathological findings were classified as chronic gastritis group, precancerous lesions group and stomach cancer group. Dietary Inflammatory Index (DII) scores were calculated based on the frequency of food occurrences in the questionnaire, and finally SPSS was used to calculate the correlation between variables. A total of 1162 patients were included in this study, including 668 cases of chronic gastritis, 411 cases of precancerous lesions, and 83 cases of cancer. A single factor analysis was conducted to examine the risk factors of stomach cancer, revealing a significant association between a pro-inflammatory diet and the stomach cancer odds (p value < 0.05). The results of binary classification analysis further confirmed that a pro-inflammatory diet is a risk factor for stomach cancer 【odds ratio (OR) =7.400)】. Moreover, correlation analysis demonstrated a positive correlation between the severity of gastric mucosal diseases and an inflammatory diet (including anti-inflammatory and pro-inflammatory diets) (rs=0.274, p-value < 0.001). Pro-Inflammatory diet is a risk factor for stomach cancer, and may accelerate the progression of stomach mucosal disease.

Relationship between gastric xanthoma, gastric precancerous lesions, and gastric cancer: A retrospective study.

To evaluate the relationship between gastric cancer and its precancerous lesions and gastric xanthoma. Medical records of 47 736 patients who underwent gastroscopy in our center from January 2020 to December 2021 were reviewed. Patients' age, sex, endoscopic and histopathological findings, and the presence, number and location of gastric xanthoma were recorded. To investigate the detection rate of gastric xanthoma at different stages of gastric lesions, the participants were further divided into the chronic gastritis group (n = 42 758), the precancerous lesion group (n = 3672), and the gastric cancer group (n = 1306), respectively. The overall detection rate of gastric xanthoma was 2.85%, and it was most commonly observed in the gastric antrum (52.50%). In addition, gastric xanthoma was more common in men and more likely to be single lesion. It was most detected in the precancerous lesion group (8.39%), followed by the gastric cancer group (5.44%), and least in the chronic gastritis group (2.29%). Multivariate analysis showed that gastric xanthoma was closely related to precancerous lesions (odds ratio [OR] 3.197, 95% confidence interval [CI] 2.791-3.662, P < 0.001) and gastric cancer (OR 1.794, 95% CI 1.394-2.309, P < 0.001). Gastric xanthoma is closely related to gastric precancerous lesions and gastric cancer.

STUDY ON THE PRESENCE OF OIPA AND DUPA GENES OF HELICOBACTER PYLORI IN GASTRIC CANCER PATIENTS

Objectives: To determine the percentage of Helicobacter pylori (H. pylori) carrying the outer inflammatory protein A (oipA), duodenal ulcer promotion (dupA) genes, and their relationship with endoscopic imaging, histopathology, and the risk of gastric cancer (GC). Subjects and methods: A cross-sectional study on 89 GC patients, compared with 90 patients with chronic gastritis (CG) with H. pylori infection, diagnosis based on histopathological results at Military Hospital 103 and Central Military Hospital 108 from August 2019 to May 2022. Determination of oipA, dupA genes of H. pylori by realtime-PCR technique on biopsy tissue samples of the gastric mucosa. Results: The percentage of H. pylori carrying the oipA and dupA genes was 30.2% and 10.1%, respectively. The relationship between bacterial infection harboring these 2 genes and endoscopic images and histopathology of GC has not been recorded. There was no difference in the prevalence of H. pylori carrying the oipA and dupA genes infection between the GC and CG groups (p &gt; 0.05). Conclusion: The infection of H. pylori with oipA and dupA genes positive may not increase GC risk in Vietnamese.

U-Net deep learning model for endoscopic diagnosis of chronic atrophic gastritis and operative link for gastritis assessment staging: a prospective nested case–control study

Background: The operative link for the gastritis assessment (OLGA) system can objectively reflect the stratification of gastric cancer risk in patients with chronic atrophic gastritis (CAG). Objectives: We developed a real-time video monitoring model for the endoscopic diagnosis of CAG and OLGA staging based on U-Net deep learning (DL). To further validate and improve its performance, we designed a study to evaluate the diagnostic evaluation indices. Design: A prospective nested case–control study Methods: Our cohort consisted of 1306 patients from 31 July 2021 to 31 January 2022. According to the pathological results, patients in the cohort were divided into the CAG group and the chronic non-atrophic gastritis group to evaluate the diagnostic evaluation indices. Each atrophy lesion was automatically labeled and the atrophy severity was assessed by the model. Propensity score matching was used to minimize selection bias. Results: The diagnostic evaluation indices and the consistency between OLGA staging and pathological diagnosis of the model were superior to those of endoscopists [sensitivity (89.31% versus 67.56%), specificity (90.46% versus 70.23%), positive predictive value (90.35% versus 69.41%), negative predictive value (89.43% versus 68.40%), accuracy rate (89.89% versus 68.89%), Youden index (79.77% versus 37.79%), odd product (79.23 versus 4.91), positive likelihood ratio (9.36 versus 2.27), negative likelihood ratio (0.12 versus 0.46)], areas under the curves (AUC) (95% CI) (0.919 (0.893–0.945) versus 0.749 (0.707–0.792), p &lt; 0.001) and kappa (0.816 versus 0.291)]. Conclusion: Our study demonstrated that the DL model can assist endoscopists in real-time diagnosis of CAG during gastroscopy and synchronous identification of high-risk OLGA stage (OLGA stages III and IV) patients. Trial registration: ChiCTR2100044458.

Differential Long Non-Coding RNA Expression Analysis in Chronic Non-Atrophic Gastritis, Gastric Mucosal Intraepithelial Neoplasia, and Gastric Cancer Tissues.

Gastric cancer (GC) has a high incidence worldwide, and when detected, the majority of patients have already progressed to advanced stages. Long non-coding RNAs (lncRNAs) have a wide range of biological functions and affect tumor occurrence and development. However, the potential role of lncRNAs in GC diagnosis remains unclear. We selected five high-quality samples from each group of chronic non-atrophic gastritis, gastric mucosal intraepithelial neoplasia, and GC tissues for analysis. RNA-seq was used to screen the differentially expressed lncRNAs, and we identified 666 differentially expressed lncRNAs between the chronic non-atrophic gastritis and GC groups, 13 differentially expressed lncRNAs between the gastric mucosal intraepithelial neoplasia and GC groups, and 507 differentially expressed lncRNAs between the chronic non-atrophic gastritis and gastric mucosal intraepithelial neoplasia groups. We also identified six lncRNAs (lncRNA H19, LINC00895, lnc-SRGAP2C-16, lnc-HLA-C-2, lnc-APOC1-1, and lnc-B3GALT2-1) which not only differentially expressed between the chronic non-atrophic gastritis and GC groups, but also differentially expressed between the gastric mucosal intraepithelial neoplasia and GC groups. Furthermore, RT-qPCR was used to verify the differentially co-expressed lncRNAs. LncSEA was used to conduct a functional analysis of differentially expressed lncRNAs. We also predicted the target mRNAs of the differentially expressed lncRNAs through bioinformatics analysis and analyzed targeting correlations between three differentially co-expressed lncRNAs and mRNAs (lncRNA H19, LINC00895, and lnc-SRGAP2C-16). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to explore the functions of target mRNAs of differentially expressed lncRNAs. In conclusion, our study provides a novel perspective on the potential functions of differentially expressed lncRNAs in GC occurrence and development, indicating that the differentially expressed lncRNAs might be new biomarkers for early GC diagnosis.

Alterations in the saliva microbiome in patients with gastritis and small bowel inflammation

The oral microbiome is an important part of the human microbiome. Accumulating data have shown that oral microbiome alterations are closely related to multiple human diseases. However, salivary microbiota distributions remain unclear in patients with gastritis and small bowel inflammation. Magnetically guided capsule endoscopy (MGCE) is a noninvasive diagnostic tool for patients with gastritis and small bowel inflammation. Herein, we analysed the alterations in saliva microbiota in the normal, small intestinal inflammation and chronic gastritis groups through 16S rRNA gene amplicon sequencing. We found that the abundance of Lactobacillaceae was dramatically higher in chronic gastritis group than healthy individuals (p = 0.001). The levels of Porphyromonas and Faecalibaculum in gastritis samples were increased (p = 0.028; p = 0.006), and the enrichments of Faecalibaculum and Kosakonia in small intestine inflammation samples were elevated (p < 0.001; p = 0.002) compared to those in normal individuals. Our findings clarify the saliva microbiota components and their importance of specific bacteria in gastritis and small bowel inflammation.

Histopathologic findings on removed stomach after sleeve gastrectomy. Do they influence the outcome?

Little is known about the role of chronic gastritis on weight loss after laparoscopic sleeve gastrectomy (LSG). This study aims to investigate the relationship between histopathologic findings of gastric specimens, excess weight loss (% EWL), and excess BMI loss (% EBL) at 6 and 12 months follow up after LSG. We retrospectively reviewed the clinical records of 95 patients who had undergone LSG between January 2017 and December 2019. Based on the histopathological findings of gastric resection specimens, patients were divided into those with chronic gastritis (CG) and those without chronic gastritis (NoCG) and compared for their % EWL and % EBL at 6 and 12 months. The mean BMI was 44.74 kg/m2 in the CG group and 44.14 kg/m2 in the NoCG group. At 6 months follow up, the CG group had a mean % EWL of 45.7 and % EBL of 40.5, while NoCG had a mean % EWL of 51.1 and % EBL of 46.7. After 1-year follow-up, the CG group had a mean % EWL of 53.1 and a % EBL of 44.8, while the NoCG group had a % EWL of 54.1 and % EBL of 44. This observational study does not support the hypothesis that the occurrence of chronic gastritis can affect postoperative % EWL and % EBL.

Fecal calprotectin levels used as a noninvasive method for screening for chronic gastritis in pediatric patients. A descriptive study.

Gastritis consists of inflammation of the gastric mucosa and is one of the main causes of dyspeptic symptoms in children. To investigate the presence of inflammation by evaluating fecal calprotectin (FC) in children diagnosed with chronic gastritis. Descriptive study in Pediatric Gastroenterology Department of Ondokuz Mayis University Hospital in Turkey. Between January 2016 and July 2018, FC levels were compared retrospectively in children with chronic gastritis (histopathology-based diagnosis), patients with inflammatory bowel disease (IBD) and healthy children. A total of 67 chronic gastritis patients (61.2% girls) with a mean age of 13.09 ± 3.5 years were evaluated. The mean FC levels were 153.4 μg/g in the chronic gastritis group, 589.7 μg/g in the IBD group and 43.8 μg/g in the healthy group. These levels were higher in chronic gastritis patients than in healthy individuals (P = 0.001) and higher in IBD patients than in the other two groups (P < 0.001). The FC level in the patients with chronic active gastritis (156.3 μg/g) was higher than in those with chronic inactive gastritis (150.95 μg/g) (P = 0.011). Among the patients with chronic active gastritis, the FC level was significantly higher in Helicobacter pylori-positive individuals than in negative individuals (P = 0.031). We confirmed the association between increased FC and chronic gastritis. Elevated FC levels may be seen in patients with chronic active gastritis. In order to be able to use FC as a screening tool for chronic gastritis, further studies in a larger study group are needed.

Serum exosomal miR-122-5p, GAS, and PGR in the non-invasive diagnosis of CAG.

ObjectiveThe aim of this study was to integrate the serum exosomal miRNA miR-122-5p with canonical serological biomarkers for the non-invasive screening of chronic atrophic gastritis (CAG) patients.MethodsmiR-122-5p and U6 were amplified by the quantitative reverse transcription polymerase chain reaction (RT-qPCR), gastrin (GAS), pepsinogen I (PG-I), and PG-II and were measured by ELISA. The area under the receiver operating characteristic (ROC) curves and their correlation were analyzed.ResultsIn the present study, GAS level and PG-I/PG-II ratio (PGR) were increased in CAG group, but there was no significant difference in PG-I or PG-II levels between CAG group and chronic non-atrophic gastritis (CNAG) group. Only GAS level and PG-I/PG-II ratio were significantly correlated with atrophy, and not any other clinicopathologic factors. Expression of hsa-miR-122-5p positively correlated with GAS level, PG-I level, and PGR, while it negatively correlated with PG-II level; however, none of them had significant difference. The combination of GAS, PGR, and hsa-miR-122-5p presented as a better model for non-invasive screening of CAG compared to others.ConclusionThese results suggested that serum exosomal hsa-miR-122-5p combined with GAS and PGR would elevate accuracy and specificity in non-invasive screening of CAG.

Characteristics of gastric mucosa microbiota in children with chronic gastritis and duodenal ulcer

Objective: To investigate the differences of gastric mucosa microbiota between children with chronic gastritis and duodenal ulcer under the condition of Helicobacter pylori (Hp) infection. Methods: This prospective cohort study involved 57 children with Hp infection diagnosed by gastric endoscopy who were admitted to the Children's Hospital of Zhejiang University School of Medicine due to "abdominal pain, abdominal distension and vomiting" between January 2018 to August 2018. According to gastroscopy and pathological examination, the children were divided into chronic gastritis group and duodenal ulcer group. Gastric mucosa from Hp infected patients were sampled, and the flora DNA was analyzed by high-throughput sequencing. The statistical difference of α diversity, β diversity between two groups were analyzed. The relative abundance of the two groups in each taxonomic level was analyzed statistically. T test, Rank sum test or χ2 test was used for comparison between the two groups. Results: A total of 57 children diagnosed with Hp infection were enrolled in this study, including 42 cases of chronic gastritis (the age was (9.3±2.8) years, 22 males and 20 females) and 15 cases of duodenal ulcer (the age was (11.1±3.3) years, 9 males and 6 females). Alpha diversity index Chao and ACE in Hp infected chronic gastritis group were significantly higher than those in Hp infected duodenal ulcer group (217±50 vs. 183±64, t=2.088, P=0.009;218±47 vs. 192±76, t=1.566, P=0.016, respectively). The Beta-diversity index such as nonmetric multidimensional scaling (NMDS) analysis were significantly different in the two groups (analysis of similarity R=0.304, P=0.028). Among the main bacteria genera, there were 6 genera with significant differences between the two groups, which were Prevotella (0.190% (0.008%-1.983%) vs. 0.021% (0.005%-2.398%), Z=-2.537, P=0.011), Alloprevotella (0.097% (0.010%-0.813%) vs. 0.015% (0.003%-0.576%), Z=-2.492, P=0.013), Haemophilus (0.109% (0.004%-0.985%) vs. 0.014% (0.004%-0.356%), Z=-2.900, P=0.004), Neisseria (0.074% (0.004%-0.999%) vs. 0.024% (0.003%-0.255%), Z=-2.718, P=0.007), Streptococcus (0.166% (0.008%-1.869%) vs. 0.045% (0.006%-0.879%), Z=-2.537, P=0.010), and an unclassified-Microbacteriaceae (0.214% (0.060%-1.762%) vs. 0.117% (0.010%-0.954%), Z=-2.120, P=0.034). Linear discriminant analysis (LDA) effect sized analysis showed that at the genus level, only Prevotella was significantly enriched in the duodenal ulcer group (LDA=2.90, P=0.010), while Streptococcus, Neisseria and Haemophilus were significantly enriched in the chronic gastritis group (LDA=2.83, 2.82, 2.69, P=0.011, 0.007, 0.004, respectively). Conclusions: The gastric mucosal microbiota in duodenal ulcer associated with Hp is significantly different from that in chronic gastritis. Hp may promote the occurrence of peptic ulcer together with gastric microbiota.

Expression of Wnt3, β-catenin and MMP-7 in gastric cancer and precancerous lesions and their correlations with Helicobacter pylori infection.

To compare the expression of the Wnt signaling-associated proteins (Wnt3, β-catenin, MMP-7) in gastric cancer and precancerous lesions with positive and negative Helicobacter pylori (H.pylori, Hp) infection, and to further explore the mechanisms underlying the Wnt signaling pathway involving in the formation of gastric cancer and its relationship with Hp infection. The complete paraffin samples with pathologically confirmed diagnosis, who came from the First Hospital of Changsha from January 2018 to April 2020, were collected. All samples were randomly divided into a gastric cancer group (n=57), a precancerous lesion group (n=84), and a chronic superficial gastritis group (n=25). Improved Giemsa staining was used to detect Hp infection, and according the results of Hp infection the above groups were divided into a Hp positive subgroup and a negative subgroup. The expressions of Wnt3, β-catenin and MMP-7 were examined with immunohistochemistry. The Wnt3, β-catenin, and MMP-7 were highly expressed in the gastric cancer group and the gastric precancerous lesion group. The Wnt3 and MMP-7 were highly expressed in cytoplasm, and β-catenin showed a tendency of cell membrane transferring to cytoplasm and nucleus, which was characterized by "nuclear translocation". The positive rates of the Wnt3, β-catenin, and MMP-7 expressions in the gastric cancer group were higher than those in the precancerous lesion group and the chronic superficial gastritis group (all P<0.05), which showed a gradually increasing trend with the deterioration of differentiation degree. In addition, the expressions of Wnt3, β-catenin, and MMP-7 in the Hp positive subgroup in the gastric cancer group and the precancerous lesion group were higher than those in the Hp negative subgroup (all P<0.05). Aberrant activation of Wnt signaling pathway is involved in the occurrence and development of precancerous lesions and gastric cancer, and which is related with Hp infection. Meanwhile, the Wnt3, β-catenin and MMP-7 may be used as molecular markers for early diagnosis of gastric cancer and indicators to judge the degree of differentiation and malignancy of gastric cancer.

Bile reflux is an independent risk factor for precancerous gastric lesions and gastric cancer: An observational cross‐sectional study

ObjectiveTo identify whether bile reflux on endoscopy and other related variables are risk factors for precancerous gastric lesions and gastric cancer (GC).MethodsA multicenter, cross‐sectional and observational study was conducted in five centers in China from June to October 2019, 1162 patients were recruited and divided into the chronic gastritis (CG), the precancerous lesion (low‐grade intraepithelial neoplasia and intestinal metaplasia), and GC groups (including high‐grade intraepithelial neoplasia). All participants underwent detailed interviews, endoscopy and biopsy, and completed questionnaires. Odds ratio and 95% confidence interval were calculated with multivariate logistic regression models with or without adjustment for Helicobacter pylori infection.ResultsWe recruited 668 patients with CG, 411 with precancerous lesions and 83 with GC. By comparing the CG and precancerous lesion groups, independent risk factors for cancerous gastric lesions were the grade of bile reflux, patient's age, dietary habits and family history of GC. Similar results were obtained when comparing the CG and GC groups. In addition, bile reflux was confirmed as an independent risk factor for progression from precancerous lesions to cancer.ConclusionsBile reflux on endoscopy as well as age, dietary habits and a family history of GC were independent risk factors for the development of precancerous gastric lesions and GC.

The Diagnostic Value of Serum Gastrin-17 and Pepsinogen for Gastric Cancer Screening in Eastern China.

Objective To evaluate the diagnostic value of gastrin-17 (G-17) and pepsinogen (PG) in gastric cancer (GC) screening in China, especially eastern China, and to determine the best diagnostic combination and threshold (cutoff values) to screen out patients who need gastroscopy. Methods The serum concentrations of G-17 and pepsinogen I and II (PGI and PGII) in 834 patients were analyzed, and the PGI/PGII ratio (PGR) was calculated. According to pathological results, patients can be divided into chronic nonatrophic gastritis (NAG)/chronic atrophic gastritis (CAG)/intraepithelial neoplasia (IN)/GC groups. The differences in G-17, PG, and PGR in each group were analyzed, and their values in GC diagnosis were evaluated separately and in combination. Results There were differences in serum G-17, PGII, and PGR among the four groups (NAG/CAG/IN/GC) (P ≤ 0.001). In total, 54 GC cases were diagnosed, of which 50% were early GC. There was no significant difference in the PGI levels among the four groups (P = 0.377). NAG and CAG composed the chronic gastritis (CG) group. The G-17 and PGII levels in the IN and GC groups were higher than those in the CG group (both P ≤ oth C), while the PGR levels were lower (P ≤ lower). When distinguishing NAG from CAG, the best cutoff value for G-17 was 9.25 pmol/L, PGII was 7.06 μg/L, and PGR was 12.07. When distinguishing CG from IN, the best cutoff value for G-17 was 3.86 pmol/L, PGII was 11.92 μg/L, and PGR was 8.26. When distinguishing CG from GC, the best cutoff value for G-17 was 3.89 pmol/L, PGII was 9.16 μg/L, and PGR was 14.14. The sensitivity, specificity, accuracy, and positive and negative predictive values of G-17/PGII/PGR for GC diagnosis were 83.3%/70.4%/79.6%, 51.8%/56.3%/47.8%, 53.8%/57.2%/49.9%, 10.7%/10.9%/9.6%, and 97.8%/96.5%/97.1%, respectively. The sensitivity, specificity, accuracy, and positive predictive and negative predictive values of PGII/G-17 vs. PGR/G-17 vs. PGR/PGII in the diagnosis of GC were 63.0% vs. 70.4% vs. 64.8%, 70.5% vs. 70.1% vs. 60.4%, 70.0% vs. 70.1% vs. 60.7%, 12.9% vs. 14.0% vs. 10.2%, and 96.5% vs. 97.2% vs. 96.1%, respectively. Conclusion The PGII and G-17 levels in patients with gastric IN and GC were significantly increased, while the serum PGR level was significantly decreased. Serological detection is effective for screening GC. The combination of different markers can improve the diagnostic efficiency. The highest diagnostic accuracy was G-17 combined with PGR, and the best cutoff values were G − 17 > 3.89 pmol/L and PGR < 14.14.

Predictors for development of complete and incomplete intestinal metaplasia (IM) associated with H. pylori infection: A large-scale study from low prevalence area of gastric cancer (IM-HP trial).

BackgroundGastric intestinal metaplasia (IM) is precancerous lesion of gastric cancer related to H. pylori infection. There has been limited data about IM and associated risk factors. This study aimed to determine risk factors related to development of IM to guide proper management.Methods1,370 patients undergoing UGI endoscopy at Thammasat University Hospital, Thailand were included between January 2018-August 2019. Patients’ data including baseline characteristics, laboratory results, and histopathology from medical database were extensively reviewed. Immunohistochemical staining for p53 expression from gastric biopsies was also performed.ResultsOverall H. pylori prevalence was 43.8%. Mean age was 60.7 years and 45% of whom were males. Chronic gastritis was observed in 1,064(77.7%) patients, while 223(16.3%) had IM. Of 223 patients with IM, 194(87%) patients had complete IM, while 29 (13%) had incomplete IM. In groups of complete and incomplete IM, current H. pylori infection rates were 66.5% and 58.6%, respectively. The BMI of incomplete IM group(27.4) was significantly higher than BMI of complete IM group (23.6). Overweight and obese patients (BMI ≥23 kg/m2) were significantly associated with higher risk for the development of incomplete IM (OR 3.25; 95%CI 1.14–9.27, p = 0.027). Males, age >50 years, and current H. pylori infection were significantly higher in IM than chronic gastritis group with OR 1.43 (95%CI 1.01–2.03, p = 0.048), OR 1.67 (95% CI 1.08–2.57, p = 0.021), and OR 3.14 (95% CI 2.29–4.30, p<0.001), respectively. During 20 months of study, there were 15 patients (1.1%) diagnosed with gastric cancer and 1-year survival rate was only 60%.ConclusionsMales, age >50 years, and current H. pylori infection are significant predictors for the presence of intestinal metaplasia. BMI might be beneficial for using as a predictive risk factor to reduce the development of incomplete intestinal metaplasia. H. pylori eradication could be an effective way to prevent the development of gastric precancerous lesions.

Tu1508 PREDICTORS FOR DEVELOPMENT OF COMPLETE AND INCOMPLETE INTESTINAL METAPLASIA (IM) ASSOCIATED WITH HELICOBACTER PYLORI INFECTION: A LARGE-SCALE STUDY FROM LOW PREVALENCE AREA OF GASTRIC CANCER (IM-HP TRIAL)

Gastric intestinal metaplasia (IM) is a precancerous lesion of gastric cancer related to Helicobacter pylori (H. pylori) infection. Until now, there has been limited data about IM prevalence and associated risk factors in Thai people. This study aimed to determine risk factors related to the development of IM to guide proper management in Thailand. 1,117 dyspeptic patients undergoing upper gastrointestinal endoscopy in Thammasat University Hospital, Thailand were enrolled between April 2018 and August 2019. Patients’ data including baseline characteristics, laboratory results, and histopathology of gastric biopsies from medical database were extensively reviewed. 1,117 patients had overall H. pylori prevalence of 44.8% and the mean age was 60.6 years and 44.7% of whom were males. 862 (77.2%) patients demonstrated chronic gastritis, while 209 (18.7%) had IM. There were 180 (16.1%) patients with complete IM and 29 (2.6%) with incomplete IM. In groups of complete and incomplete IM, current H. pylori infection rates were 66.1%, and 58.6%, respectively (OR 0.73; 95% CI 0.33-1.62, p = 0.434). The mean body mass index (BMI) of incomplete IM group (27.3) was significantly higher than BMI of complete IM group (23.7) (OR 1.13; 95% CI 1.04-1.23, p = 0.003). Age >45 years, current H. pylori infection, and family history of gastric cancer were significantly higher in IM than chronic gastritis group with OR 1.90 (95% CI 1.04-3.45, p = 0.036), OR 2.94 (95% CI 2.10-4.11, p <0.001), and OR 5.36 (95% CI 1.11-26.01, p = 0.037), respectively, as demonstrated in table 1 and 2. There was no difference of laboratory result including complete blood count, plasma glucose, tumor markers (CEA and CA19-9) between complete and incomplete IM groups. During 16 months of study, there were 12 patients (1.1%) diagnosed with gastric cancer and 2 of them had history of prior IM along with adenocarcinoma on their gastric pathology. The 1-year survival rate of 12 gastric cancer patients was as low as 50%. Age >45 years, current H. pylori infection, and family history of gastric cancer are significant predictors for the presence of intestinal metaplasia. Body mass index might be beneficial for using as a predictive risk factor to reduce the development of incomplete intestinal metaplasia. H. pylori eradication could be an effective way to prevent the development of gastric precancerous lesions.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Characterization and strong risk association of TLR2 del -196 to -174 polymorphism and Helicobacter pylori and their influence on mRNA expression in gastric cancer.

BACKGROUNDToll-like receptor-2 (TLR2) is responsible for recognizing Helicobacter pylori (H. pylori) and activating the immune response. Polymorphisms in TLR2 may modulate gastric carcinogenesis.AIMTo evaluate whether the TLR2 19216T/C (rs3804099) and TLR2 -196 to -174 ins/del (rs111200466) polymorphisms contribute to gastric carcinogenesis in the Brazilian population, and to determine the influence of both polymorphisms and H. pylori infection on TLR2 mRNA expression.METHODSDNA was extracted from 854 peripheral blood leukocyte or gastric tissue samples [202 gastric cancer (GC), 269 chronic gastritis (CG), and 383 control/healthy (C)] and genotyped by allele-specific PCR or restriction fragment length polymorphism (RFLP)-PCR. Quantitative polymerase chain reaction by TaqMan® assay was used to quantify TLR2 mRNA levels in fresh gastric tissues (48 GC, 36 CG, and 14 C).RESULTSRegarding the TLR2 -196 to -174 polymorphism, the ins/del and del/del genotypes were associated with a higher risk of GC by comparison with the C in all of the analyzed inheritance models (codominant, dominant, recessive, overdominant and log-additive; P < 0.0001). Similarly, an increased risk was observed when comparing the GC and CG groups [codominant (P < 0.0001), dominant (P < 0.0001), recessive (P = 0.0260), overdominant (P < 0.0001) and log-additive (P < 0.0001)]. In contrast, TLR2 19216T/C was associated with a protective effect in the GC group compared to the C group [dominant (P = 0.0420) and log-additive (P = 0.0300)]. Regarding the association of polymorphisms with H. pylori infection, individuals infected with H. pylori and harboring the TLR2 -196 to -174 ins/del polymorphism had an increased risk of gastric carcinogenesis [codominant (P = 0.0120), dominant (P = 0.0051), overdominant (P = 0.0240) and log-additive (P = 0.0030)], while TLR2 19216T/C was associated with a protective effect [codominant (P = 0.0039), dominant (P < 0.0001), overdominant (P = 0.0097) and log-additive (P = 0.0021)]. TLR2 mRNA levels were significantly increased in the GC group (median RQ = 6.95) compared to the CG group (RQ = 0.84, P < 0.0001) and to the normal mucosa group (RQ = 1.0). In addition, both H. pylori infection (P < 0.0001) and the presence of the polymorphic TLR2 -196 to -174del (P = 0.0010) and TLR2 19216 C (P = 0.0004) alleles influenced TLR2 mRNA expression.CONCLUSIONThe TLR2 -196 to -174 ins/del and TLR2 19216 T/C polymorphisms are strongly associated with GC. TLR2 mRNA expression levels are upregulated in neoplastic tissues and influenced by both the presence of H. pylori and variant genotypes.