Risk Factor For Gastric Cancer Research Articles

Correlation analysis of endoscopic manifestations and eradication effect of Helicobacter pylori.

Helicobacter pylori (H. pylori) infection is the most important risk factor for gastric cancer. Eradication of H. pylori significantly reduces the incidence and mortality of gastric cancer. H. pylori resistance to antibiotics and a gradual decline in eradication rates are gaining more and more attention. Our study aimed to address the correlation between endoscopic manifestations and the eradication effect of H. pylori. We retrospectively reviewed outpatients in our hospital with H. pylori infection undergoing eradication therapy from January 2022 to March 2023. Both the primary diagnosis and eradication of H. pylori after treatment were confirmed by a 13C urea breath test. Patients were treated with a proton pump inhibitor (PPI)-based quadruple therapy. Clinical characteristics and endoscopy manifestations within 7 days before or after patients were diagnosed with H. pylori infection were analyzed. From January 2022 to March 2023, a total of 323 patients were enrolled in this study. There were 138 male patients and 185 female patients. The mean age of patients was 45.62 ± 13.04 years. The H. pylori initial eradication rate was 82.0%. Univariate analysis of factors affecting H. pylori eradication showed that sex, age, and endoscopic manifestations including diffuse redness, multiple white, and flat elevated lesions, and atrophy were significantly associated with the failure of H. pylori eradication therapy. A multivariable logistic regression model analysis of these five factors showed that patients aged over 60 years with multiple white and flat elevated lesions in the endoscopic examination are significantly less likely to eradicate H. pylori with empirical quadruple therapy. On the other hand, patients with diffuse redness were significantly more likely to eradicate H. pylori infection with empirical quadruple therapy. Our study shows that age over 60 years old, multiple white and flat elevated lesions in endoscopic examination are independent risk factors of initial H. pylori eradication failure with empirical quadruple therapy, while diffuse redness in endoscopic examination is a protective factor of initial H. pylori eradication failure with empirical quadruple therapy, while diffuse redness in endoscopic examination is a protective factor. For patients with these risk factors, a drug sensitivity test or H. pylori resistance gene mutation detection may be more appropriate. However, further mechanism studies or prospective studies are needed to prove our findings.

Comparison of different risk stratifications for gastric cancer and establishing a simplified risk-scoring model based on the Kyoto classification.

The study aims to assess the value of different risk stratifications in diagnosing early gastric cancer (GC) and explore risk factors based on Kyoto gastritis classification. This study was a single-centered cross-sectional study; all epidemiological data and endoscopic findings were obtained prospectively. To evaluate the proportion of GC in each risk stratification and to compare the diagnostic performance of different methods using the receiver operating characteristic curve, univariable and multivariable analyses were used to explore the correlation between endoscopic findings and GC. A total of 240 subjects were enrolled, and the diagnostic efficacy of the Kyoto Classification Score was similar to Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stage, and the accuracy was higher than that of the Japanese scoring system and OLGA stage. Moderate atrophy (odds ratio [OR]=3.52, 95% confidence interval [CI]: 1.52-8.16), severe atrophy (OR=4.96, 95% CI: 1.75-14.04), map-like redness (OR=9.89, 95% CI: 1.16-84.15), and xanthelasma (OR=3.57, 95% CI: 1.15-11.15) were independent risk factors for GC. The simplified Kyoto classification (area under the receiver operating characteristic [AUROC]=0.76, P=0.58) based on multivariable analysis demonstrated favorable diagnostic value compared with traditional Kyoto classification score (AUROC=0.74). This study confirms the value of the Kyoto classification score and the OLGIM stage in the risk stratification of GC. Simplified Kyoto classification is also promising in risk assessment of GC but still requires validation in the population.

Gastric Cancer Risk Factors ina Veteran Population.

Risk factors for gastric cancer in the United States are not well understood, especially in populations with a low proportion of immigrants. We conducted a matched case-control study in a Veteran Affairs Medical Center to identify risk factors for gastric cancer. Gastric cancer patients and age- and sex-matched controls were identified in a 1:4 ratio from January 1, 1997 to October 31, 2018. Demographic, medical, endoscopic, and histologic data were extracted. We performed conditional logistic regression to estimate odds ratios and 95% CIs for associations between potential risk factors and gastric cancer. Most gastric cancer cases were diagnosed on initial endoscopy (71.4%). Of these, the most common presenting stage was stage IV (40.8%). Risk factors for gastric cancer included Black and Asian race and never or current (compared to former) drinkers, although Helicobacter pylori eradication and pernicious anemia were associated with decreased risk. The high proportion of late-stage gastric cancer diagnoses highlights the need for improved risk stratification as well as screening and surveillance protocols in the U.S. population. Racial disparities among veterans in an equal-access system necessitate further investigation into the etiology of these disparities.

The global prevalence of gastric cancer in Helicobacter pylori-infected individuals: a systematic review and meta-analysis

BackgroundHelicobacter pylori is a gastrointestinal pathogen that infects around half of the world's population. H. pylori infection is the most severe known risk factor for gastric cancer (GC), which is the second highest cause of cancer-related deaths globally. We conducted a systematic review and meta-analysis to assess the global prevalence of GC in H. pylori-infected individuals.MethodsWe performed a systematic search of the PubMed, Web of Science, and Embase databases for studies of the prevalence of GC in H. pylori-infected individuals published from 1 January 2011 to 20 April 2021. Metaprop package were used to calculate the pooled prevalence with 95% confidence interval. Random-effects model was applied to estimate the pooled prevalence. We also quantified it with the I2 index. Based on the Higgins classification approach, I2 values above 0.7 were determined as high heterogeneity.ResultsAmong 17,438 reports screened, we assessed 1053 full-text articles for eligibility; 149 were included in the final analysis, comprising data from 32 countries. The highest and lowest prevalence was observed in America (pooled prevalence: 18.06%; 95% CI: 16.48 − 19.63; I2: 98.84%) and Africa (pooled prevalence: 9.52%; 95% CI: 5.92 − 13.12; I2: 88.39%). Among individual countries, Japan had the highest pooled prevalence of GC in H. pylori positive patients (Prevalence: 90.90%:95% CI: 83.61–95.14), whereas Sweden had the lowest prevalence (Prevalence: 0.07%; 95% CI: 0.06–0.09). The highest and lowest prevalence was observed in prospective case series (pooled prevalence: 23.13%; 95% CI: 20.41 − 25.85; I2: 97.70%) and retrospective cohort (pooled prevalence: 1.17%; 95% CI: 0.55 − 1.78; I 2: 0.10%).ConclusionsH. pylori infection in GC patients varied between regions in this systematic review and meta-analysis. We observed that large amounts of GCs in developed countries are associated with H. pylori. Using these data, regional initiatives can be taken to prevent and eradicate H. pylori worldwide, thus reducing its complications.

Association between Socioeconomic Factors and the Risk of Gastric Cancer Incidence: Results from an Ecological Study.

Gastric cancer (GC), one of the most common cancer worldwide, remains the third leading cause of cancer-related mortality. The etiology of GC may arise from genetic and environmental factors. This study aimed to determine the association between GC incidence and socioeconomic status in Iran. An ecological study was designed to investigate the relationship between socioeconomic factors and the risk of GC incidence. The data of socioeconomic variables such as income changes, unemployment rate, urbanization ratio, inflation rate, and air pollution changes in 31 provinces were collected from the Statistical Center of Iran, and the data of GC of 31 provinces were provided from the Iranian National Population-based Cancer Registry (INPCR). Data from 2014 to 2017 was analyzed using panel data analysis, the fixed effects model by EViews software. Panel data model was suitable for the present study. Results showed that there was a positive and significant relationship between GC incidence and socioeconomic factors including income changes (P≤ 0.001), unemployment rate (P≤0.01), inflation rate (P≤ 0.05), and air pollution changes (P≤ 0.001). The urbanization ratio showed a negative relationship and was not statistically associated with GC incidence (P> 0.05). Our findings suggest a positive and significant association between socioeconomic status and GC incidence, proposing a GC risk factor. The key public health policies and welfare policies' priority should therefore be to schedule for the GC management.

Efficacy of quadruple therapy with clarithromycin based on faecal molecular antimicrobial susceptibility tests as first-line treatment for Helicobacter pylori infection: a protocol of a single-centre, single-blind, randomised clinical trial in China

IntroductionHelicobacter pylori is the most well-known risk factor for gastric cancer. Antibiotic resistance is the main reason for the failure of H. pylori eradication, and understanding the antibiotic resistance before...

Gastric troubles in Iran: The role of social and economic factors in Helicobacter pylori infection.

Helicobacter pylori infection is a major risk factor for gastric cancer in Iran, but the impact of socioeconomic factors on its prevalence is poorly understood. This study aimed to assess the socioeconomic inequalities and risk factors associated with H. pylori infection in Iran. This cross-sectional study was conducted based on the PERSIAN cohort study. A total of 20460 individuals aged 35 to 70 years in Ardabil, Iran were included in the study. H. pylori infection was determined based on stool tests and clinical records. Multilevel logistic regression models with random intercepts at household and community levels were used to identify risk factors associated with H. pylori prevalence. The concentration index (CIn) and concentration curve (CC) were employed to assess socioeconomic-related inequality. In this study, 70.4% (CI 69.6-71.0) of the participants were infected with H. pylori, with a higher prevalence in women (71.2%) than men (69.6%). Age (OR: 1.37, CI: 1.17-1.61), sex (OR: 1.20, CI: 1.12-1.28), level of education (OR: 1.33, CI: 1.17-1.49), cardiac disease (OR: 1.32, CI:1.18-1.46), and BMI groups (OR: 2.49, CI: 1.11-5.58) were significantly associated with H. pylori infection based on the multivariable logistic regression. The results of the CIn and CC indicated that H. pylori were more prevalent among economically disadvantaged groups (CIn: -0.1065; [-0.1374 to -0.0755]). The prevalence of H. pylori in Iran is higher than in other developing countries, and significant socioeconomic inequality exists between the poor and the rich. To reduce the rate of gastric cancer, socio-economic and demographic factors, especially the poor and people with low levels of education, should be considered.

Modeling Epidemiology Data with Machine Learning Technique to Detect Risk Factors for Gastric Cancer.

Gastric cancer (GC) ranks as the 7th most common cancer worldwide and a leading cause of cancer mortality. In Iran, stomach malignancies are the most common fatal cancers with higher than world average incidence. In recent years, methods like machine learning that provide the opportunity of merging health issues with computational power and learning capacity have caught considerable attention for prediction and diagnosis of diseases. In this study, we aimed to model GC data to find risk factors and identify GC cases in Golestan Cohort Study (GCS), using gradient boosting as a machine learning technique. Since the GC class (280) was smaller than not-GC (49,467), "Synthetic Minority Oversampling Technique" was used to balance the dataset. Seventy percent of the data was used to train the gradient boosting algorithm and find effective factors on gastric cancer, and the remaining 30% was used for accuracy assessment. Our results indicated that out of 19 factors, age, social economical status, tea temperature, body mass index, gender, and education were the top six effective factors with impact rates of 0.24, 0.16, 0.13, 0.13, and 0.07, respectively. The trained model classified 70 out of 72 GC patients in the test set, correctly. The results indicate that this model can effectively detect gastric cancer (GC) by utilizing important risk factors, thus avoiding the need for invasive procedures. The model's performance is reliable when provided with an adequate amount of input data, and as the dataset expands, its accuracy and generalization improve significantly. Overall, the trained system's success stems from its ability to identify risk factors and identify cancer patients.

Gastric Cancer Epidemiology: Current Trend and Future Direction

Gastric cancer (GC) is a significant global public health problem. It is the third leading cause of cancer-related mortality despite its decline in incidence since the past five decades. The incidence of GC varies between regions, and this heterogeneity is attributed to multi-factors, including infectious, environmental, and genetic traits. Most of the GC cases are linked to Helicobacter pylori (H. pylori) infection. Understanding the etiology, epidemiology, and risk factors of GC is necessary for the prevention and targeted treatment of the disease. In this study, we synthesized published studies, including data from the “International Agency for Research on Cancer GLOBOCAN” to narratively provide an updated overview of the recent global trends, etiology, known risk factors, pathogenesis, hallmarks, treatment, and prevention of GC. One area that significantly advanced GC research was understanding the mechanisms by which H. pylori colonizes humans and mediates physiological, microbiological, immune, and histologic features of the gut. However, there are still gaps present in understanding the molecular mechanisms underlying the initiation and progression of GC.

The effect of phytochemicals in N-methyl-N-nitro-N-nitroguanidine promoting the occurrence and development of gastric cancer.

Gastric cancer is a common malignant tumor of the digestive tract, with a low early diagnosis rate. N-methyl-N-nitro-N-nitroguanidine (MNNG) is one of the main risk factors for gastric cancer. Phytochemicals are healthy active substances derived from vegetables, fruits, nuts, tea, herbal medicines and other plants. Taking phytochemicals is a very promising strategy for the prevention and treatment of gastric cancer. Many studies have proved that phytochemicals have protective effects on MNNG induced gastric cancer via inhibiting cell proliferation, enhancing immunity, suppressing cell invasion and migration, inducing apoptosis and autophagy, blocking angiogenesis, inhibiting Helicobacter pylori infection as well as regulating metabolism and microbiota. The intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer have attracted more and more attention. In order to better study and explore the role, advantages and challenges of phytochemicals in MNNG induced gastric cancer, we summarized the intervention and therapeutic effects of phytochemicals in MNNG induced gastric cancer. This review may help to further promote the research and clinical application of phytochemicals in MNNG induced gastric cancer, and provide some new insights.

Identification of PTPN20 as an innate immunity-related gene in gastric cancer with Helicobacter pylori infection.

Gastric cancer (GC) is among the deadliest diseases with countless incidences and deaths each year. Helicobacter pylori (Hp) is the primary type of microbe that colonizes the stomach. In recent years, increasing evidence has demonstrated that Hp infection is one of the main risk factors for GC. Elucidating the molecular mechanism of how Hp leads to GC will not only benefit the treatment of GC, but also boost the development of therapeutics for other gastric disorders caused by Hp infection. In this study, we aimed to identify innate immunity-related genes in GC and investigate their potentials as prognostic markers and therapeutic targets for Hp-related GC. Firstly, we analyzed the differentially expressed innate immunity-related genes in GC samples from the TCGA database. Then prognostic correlation analysis was carried out to explore the prognostic value of these candidate genes. By combing transcriptome data, somatic mutation data, and clinical data, co-expression analysis, functional enrichment analysis, tumor mutational burden analysis, and immune infiltration analysis were performed to reveal the pathological relevance of the candidate gene. Finally, ceRNA network was constructed to identify the genes and pathways for the regulation of the candidate gene. We revealed that protein tyrosine phosphatase non-receptor type 20 (PTPN20) is a significant prognostic marker in Hp-related GC. Thus, PTPN20 levels have the potential to efficiently predict the survival of Hp-related GC patients. In addition, PTPN20 is associated with immune cell infiltration and tumor mutation burden in these GC patients. Moreover, we have also identified PTPN20-related genes, PTPN20 protein-protein interactions, and the PTPN20 ceRNA network. Our data suggest that PTPN20 may have critical functions in Hp-related GC. Targeting PTPN20 may be a promising way to treat Hp-related GC.

P-414 Gastric cancer risk factors knowledge in Mexican population. LEGACy 3A

P-414 Gastric cancer risk factors knowledge in Mexican population. LEGACy 3A

Knowledge and Awareness About Gastric Cancer Among the General Population in Al-Baha City, Saudi Arabia.

Background Gastric cancer is a significant health concern worldwide, and its incidence varies across different populations. This study aimed to assess the level of knowledge and awareness of gastric cancer among the general population in Al-Baha City,Saudi Arabia. Methodology This is a cross-sectional study that was conducted amongthe residents of Al-Baha city older than 18 years. The study was conducted based on a questionnaire that has been developed by a previous study. Data were initially recorded in an Excel sheet before being exported to the SPSS program, version 25 for data analysis. Results The survey included 426 respondents from Al-Baha city, Saudi Arabia, with 56.8% being females and the majority being in the age groups (21-30 years). Alcohol consumption (mean=4.5, SD= 0.77), smoking cigarettes or Shisha (mean= 4.38, SD=0.852), family history of gastric cancer (mean= 4, SD=1.008), a past medical history of gastric cancer(mean= 3.99, SD=0.911), stomach ulcer (mean=3.76, SD=0.898), and consumption of smoked food (mean= 3.69, SD=0.956) are the most widely recognized risk factors. The most highly recognized symptoms are gastrointestinal bleeding (mean= 4.03, SD=0.875), abdominal lump (mean= 3.94, SD=0.926), weight loss (mean= 3.93, SD=0.963), recurrent nausea and vomiting (mean=3.76, SD=0.956), and abdominal pain (mean= 3.57, SD=0.995). The study also identified several subgroups of the population that may benefit fromtargeted educational programs, including individuals in the age group of 41-50 years and those in non-medical occupations. Conclusion The study found that participants had a moderate level of knowledge about therisk factorsand symptoms of gastric cancer, with significant variability among different subgroups of the population. Further research is needed to investigate the prevalence and risk factors of gastric cancer in Saudi Arabia and other similar populations, to develop effective prevention and management strategies for this disease.

Inhibitory effect of herbal compounds on the Oxygen-insensitive NADPH nitro reductase enzyme of metronidazole-resistant Helicobacter pylori

Helicobacter pylori is a significant risk factor for chronic gastritis, gastric ulcers, and gastric cancer. The purpose of this article is to investigate the potential impact of fifty herbal compounds derived from Ginger and Parsley plants, known for their antibacterial properties on the Oxygen-insensitive NADPH nitro reductase enzyme of metronidazole-resistant H. pylori. In the present study, the information on the structure of compounds, the H. pylori resistant to metronidazole enzyme, myristicin, and shogaol derivatives were obtained from databases such as ZINC15, RCSB (Protein Data Bank), and PubChem, respectively. Finally, molecular docking was performed with iGemdock2.1 and Molegro Virtual Docker. After molecular docking, four out of the fifty phytocompounds showed the lowest energy and the highest number of interactions with the amino acids at the binding sites. Among these four phytocompounds, the best phytocompound was N-Vanillyloctanamide derived from Ginger. Our molecular docking study suggests that ginger can be introduced as a potential candidate to inhibit the growth of H. pylori.

FMO family may serve as novel marker and potential therapeutic target for the peritoneal metastasis in gastric cancer.

To explore the relationship between flavin-containing monooxygenases (FMOs) and peritoneal metastasis (PM) in gastric cancer (GC). TIMER 2.0 was used to perform pan-cancer analysis and assess the correlation between the expression of FMOs and cancers. A dataset from The Cancer Genome Atlas (TCGA) was used to analyze the correlation between FMOs and clinicopathological features of GC. PM is well established as the most common mode of metastasis in GC. To further analyze the correlation between FMOs and PM of GC, a dataset was obtained from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database. The results were validated by immunohistochemistry. The relationship between FMOs and PM of GC was explored, and a novel PM risk signature was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis. The regression model's validity was tested by multisampling. A nomogram was established based on the model for predicting PM in GC patients. The mechanism of FMOs in GC patients presenting with PM was assessed by conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses in TCGA and GEO datasets. Finally, the potential relationship between FMOs and immunotherapy was analyzed. The pan-cancer analysis in TCGA and GEO datasets showed that FMO1 was upregulated, while FMO2 and FMO4 were downregulated in GC. Moreover, FMO1 and FMO2 correlated positively with the T and N stage of GC in the TCGA dataset. FMO1 and FMO2 expression was a risk factor for GC (hazard ratio: 1.112 and 1.185). The overexpression of FMO1 was significantly correlated with worse disease-free-survival (DFS) and overall survival (OS). However, no relationship was found between FMO2 expression in GC and DFS and OS. PM was highly prevalent among GC patients and typically associated with a worse prognosis. FMO1 was highly expressed in GC with PM. FMO1 and FMO2 were positively correlated with PM in GC. We identified a 12-gene panel for predicting the PM risk signature by LASSO (Area Under Curve (AUC) = 0.948, 95%CI: 0.896-1.000). A 10-gene panel for PM prediction was identified (AUC = 0.932, 95%CI: 0.874-0.990), comprising FMO1 and FMO2. To establish a model for clinical application, a 7-gene panel was established (AUC = 0.927, 95% CI: 0.877-0.977) and successfully validated by multisampling. (AUC = 0.892, 95% CI: 0.878-0.906). GO and KEGG analyses suggest that FMO1 and FMO2 regulate the extracellular matrix and cell adhesion. FMO1 and FMO2 were positively correlated with the immune score of GC, and their expression was associated with the infiltration of immune cells. PM in GC is strongly correlated with FMOs. Overall, FMO1 and FMO2 have huge prospects for application as novel diagnostic and therapeutic targets.

The TLR/MyD88 signalling cascade in inflammation and gastric cancer: the immune regulatory network of Helicobacter pylori.

Helicobacter pylori-induced chronic gastritis represents a well-established risk factor for gastric cancer (GC). However, the mechanism by which chronic inflammation caused by H. pylori induces the development of GC is unclear. H. pylori can influence host cell signalling pathways to induce gastric disease development and mediate cancer promotion and progression. Toll-like receptors (TLRs), as pattern recognition receptors (PRRs), play a key role in the gastrointestinal innate immune response, and their signalling has been implicated in the pathogenesis of an increasing number of inflammation-associated cancers. The core adapter myeloid differentiation factor-88 (MyD88) is shared by most TLRs and functions primarily in H. pylori-triggered innate immune signalling. MyD88 is envisioned as a potential target for the regulation of immune responses and is involved in the regulation of tumourigenesis in a variety of cancer models. In recent years, the TLR/MyD88 signalling pathway has received increasing attention for its role in regulating innate and adaptive immune responses, inducing inflammatory activation and promoting tumour formation. In addition, TLR/MyD88 signalling can manipulate the expression of infiltrating immune cells and various cytokines in the tumour microenvironment (TME). In this review, we discuss the pathogenetic regulatory mechanisms of the TLR/MyD88 signalling cascade pathway and its downstream molecules in H. pylori infection-induced-associated GC. The focus is to elucidate the immunomolecular mechanisms of pathogen recognition and innate immune system activation of H. pylori in the TME of inflammation-associated GC. Ultimately, this study will provide insight into the mechanism of H. pylori-induced chronic inflammation-induced GC development and provide thoughts for GC prevention and treatment strategies.

Cigarette Smoke-Induced Gastric Cancer Cell Exosomes Affected the Fate of Surrounding Normal Cells via the Circ0000670/Wnt/β-Catenin Axis.

Cigarette smoke is a major risk factor for gastric cancer. Exosomes are an important part of intercellular and intra-organ communication systems and can carry circRNA and other components to play a regulatory role in the occurrence and development of gastric cancer. However, it is unclear whether cigarette smoke can affect exosomes and exosomal circRNA to promote the development of gastric cancer. Exosomes secreted by cancer cells promote cancer development by affecting surrounding normal cells. Herein, we aimed to clarify whether the exosomes secreted by cigarette smoke-induced gastric cancer cells can promote the development of gastric cancer by affecting the surrounding gastric mucosal epithelial cells (GES-1). In the present study, we treated gastric cancer cells with cigarette smoke extract for 4 days and demonstrated that cigarette smoke promotes the stemness and EMT of gastric cancer cells and cigarette smoke-induced exosomes promote stemness gene expression, EMT processes and the proliferation of GES-1 cells. We further found that circ0000670 was up-regulated in tissues of gastric cancer patients with smoking history, cigarette smoke-induced gastric cancer cells and their exosomes. Functional assays showed that circ0000670 knockdown inhibited the promoting effects of cigarette smoke-induced exosomes on the stemness and EMT characteristic of GES-1 cells, whereas its overexpression had the opposite effect. In addition, exosomal circ0000670 was found to promote the development of gastric cancer by regulating the Wnt/β-catenin pathway. Our findings indicated that exosomal circ0000670 promotes cigarette smoke-induced gastric cancer development, which might provide a new basis for the treatment of cigarette smoke-related gastric cancer.

Effect of Helicobacter pylori on non-homologous end joining-mediated repair of proximal DNA double-strand breaks in GCV6 cells

Infection with Helicobacter pylori is the strongest known risk factor for gastric cancer, which is one of the leading causes of cancer-related mortality worldwide. H. pylori can contribute to carcinogenesis by inducing the genomic instability of infected cells through increasing accumulation of DNA double-stranded breaks (DSBs) and deregulating DSB repair systems. However, the mechanism of this phenomenon is still being elucidated. This study aims to investigate the impact of H. pylori on the efficacy of non-homologous end joining (NHEJ)-mediated repair of DSB. In this study, we used a human fibroblast cell line bearing a single copy of an NHEJ-reporter substrate stably inserted into the genome, which provides a quantitative measurement of NHEJ. Our results indicated the potential abilities of H. pylori strains to alter the NHEJ-mediated repair of proximal DSB in infected cells. In addition, we found an association between the alteration in the NHEJ efficiency, and the inflammation responses of infected cells caused by H. pylori.

Helicobacter pylori regulates stomach diseases by activating cell pathways and DNA methylation of host cells.

One of the most prevalent malignant tumors of the digestive tract is gastric cancer (GC). Age, high salt intake, Helicobacter pylori (H. pylori) infection, and a diet deficient in fruits and vegetables are risk factors for the illness. A significant risk factor for gastric cancer is infection with H. pylori. Infecting gastric epithelial cells with virulence agents secreted by H. pylori can cause methylation of tumor genes or carcinogenic signaling pathways to be activated. Regulate downstream genes' aberrant expression, albeit the precise mechanism by which this happens is unclear. Oncogene, oncosuppressor, and other gene modifications, as well as a number of different gene change types, are all directly associated to the carcinogenesis of gastric cancer. In this review, we describe comprehensive H. pylori and its virulence factors, as well as the activation of the NF-κB, MAPK, JAK/STAT signaling pathways, and DNA methylation following infection with host cells via virulence factors, resulting in abnormal gene expression. As a result, host-related proteins are regulated, and gastric cancer progression is influenced. This review provides insight into the H. pylori infection, summarizes a series of relevant papers, discusses the complex signaling pathways underlying molecular mechanisms, and proposes new approach to immunotherapy of this important disease.

Characterization of epigenetic changes during the metaplastic process by single-cell RNA sequencing

Adenocarcinomas, the most common cancers in adults, typically arise from precursor lesions that are induced by chronic injury or inflammation. As normal cells first become metaplastic and then progress to dysplasia and neoplasia, they dramatically change phenotype. Cellular identity and lineage determination throughout development are in large part regulated by epigenomic changes. Given tumorigenesis is a type of abnormal development, it follows that similar epigenetic changes occur during metaplasia; however, research on this remains relatively scant. Here, we investigate epigenetic changes in mature, digestive-enzyme-secreting gastric chief cells as they reprogram to progenitor-like, mucinous Spasmolytic Polypeptide Expressing Metaplasia (SPEM) cells. The reprogramming process occurs via a stereotypical, evolutionarily conserved sequence of cellular and molecular events known as paligenosis. We can induce chief cell paligenosis across the whole body of the stomach by intraperitoneal injections of high-dose tamoxifen (HDT), which kills acid-pumping parietal cells and causes SPEM within 48 to 72 hous. During paligenosis, cells undergo massive ultrastructural remodeling including recycling of the vast majority of the endoplasmic reticulum (ER) that they used for secreting zymogenic enzymes, and they induce expression of a number of mucins as well as progenitor-associated genes like Sox9. Thereafter, they re-enter the cell cycle to help regenerate injured tissue. To begin to identify epigenetic factors regulating the large changes in cell structure and gene expression, we are contrasting single-cell RNA-sequencing analysis of HDT-treated mouse gastric corpus versus mice without HDT treatment that does not cause SPEM. The sc-RNA-seq confirms the loss of parietal cells in both models and SPEM predominantly in HDT. We observed the induction of multiple chromatin-modifying genes during paligenosis with few such epigenetic genes expressed in mature chief cells at homeostasis, suggesting epigenetic processes might be more inert within the fully differentiated chief cells than during the dynamic paligenosis process as cells are actively rearranging phenotype. Complementing sc-RNA-seq with proteomic analysis by mass spectrometry, we have identified the DNA methyltransferase DNMT1 as a key epigenetic factor upregulated during paligenosis. DNMT1 has been previously shown to be associated with metaplasia in the stomach of patients infected with H. pylori, where both metaplasia and infection are major risk factors for gastric cancer. We confirm with immunostaining that DNMT1 is absent in chief cells at homeostasis but undergoes dramatic increase after HDT treatment. In summary, using single-cell transcriptomic methods, we are demonstrating active epigenetic-related gene expression changes during paligenosis and are following up on one DNA-modifying gene in particular, the DNA methyltransferase, DNMT1, that emerges during this process a This work was supported by funding from the NIH through the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.