Endoscopic morphology of gastric MALT lymphoma correlate with API2/MALT1 fusion and predict treatment response after helicobacter pylori eradication.

BACKGROUND: The presence of API2/MALT1 fusion in gastric mucosa-associated lymphoid tissue (MALT) lymphoma predicts poor response to Helicobacter pylori (Hp) eradication therapy. This study aimed to assess the correlation between endoscopic morphology of MALT lymphoma and API2/MALT1 fusion and evaluate treatment response to Hp eradication based on morphological subtypes. METHODS: A retrospective review was conducted on patients diagnosed with gastric MALT lymphoma between January 2011 and December 2022. Endoscopic morphology was categorized as superficial, non-superficial, or mixed type. The superficial type was further classified into gastritis superficial lesion and localized superficial lesion based on border clarity. Logistic regression models evaluated the impact of clinical and endoscopic characteristics on anti-Hp therapy effectiveness. RESULTS: Among the 114 patients included, 93 (81.6%) were Hp-positive, and API2/MALT1 fusion was detected in 58 (50.9%) cases, The superficial type was the predominate morphology (73/114, 64%). The regular arrangement of collecting venules (RAC) sign was noted in 21 (18.4%) cases. In superficial subtypes, the RAC signs were more frequently observed in localized lesion than gastritis lesion (35.6% vs. 7.1%, p = 0.01). and the superficial localized lesion was more common in individuals with positive API/MALT1 fusion than negative ones (76.9% vs. 44.1%, p = 0.01). Following Hp eradication, the remission rate for localized lesion was 34.3%, significantly lower than for gastritis lesion (66.7%, p = 0.01). Both endoscopic morphology (OR = 0.26, 95% CI 0.09-0.75) and API2-MALT1 fusion (OR = 14.29, 95% CI 4.19-48.67) impacted the efficacy of anti-Hp therapy. However, multivariate analysis identified API2-MALT1 fusion as the only independent predictor of treatment outcome (OR = 12.18, 95% CI 3.49-42.55, p < 0.001). CONCLUSION: Gastric MALT lymphomas with superficial-type morphology, particularly those with defined borders resembling early gastric cancer, were associated with API2/MALT1 fusion and a lower remission rate after Hp eradication therapy. This suggests that endoscopic morphology, along with API2/MALT1 fusion status, could help predict the therapeutic response, with API2/MALT1 fusion serving as a critical indicator of treatment resistance.

Redefining the Gastric Microbes in Promoting Gastric Tumorigenesis: The Rise of the Non-H. pylori Microbiome.

Gastric cancer remains one of the top cancers in China compared with Western countries, mainly attributed to the high rates of Helicobacter pylori infection. However, recent discoveries on the non-H. pylori gastric microbiome have led to a paradigm shift in our understanding of microbial risk factors driving gastric cancer, which will impact future screening and prevention strategies.

Intratumoral and fecal microbiota reveals microbial markers associated with gastric carcinogenesis.

Background: The relationship between dysbiosis of the gastrointestinal microbiota and gastric cancer (GC) has been extensively studied. However, microbiota alterations in GC patients vary widely across studies, and reproducible diagnostic biomarkers for early GC are still lacking in multiple populations. Thus, this study aimed to characterize the gastrointestinal microbial communities involved in gastric carcinogenesis through a meta-analysis of multiple published and open datasets. Methods: We analyzed 16S rRNA sequencing data from 1,642 gastric biopsy samples and 394 stool samples across 11 independent studies. VSEARCH, QIIME and R packages such as vegan, phyloseq, cooccur, and random forest were used for data processing and analysis. PICRUSt software was employed to predict functions. Results: The α-diversity results indicated significant differences in the intratumoral microbiota of cancer patients compared to non-cancer patients, while no significant differences were observed in the fecal microbiota. Network analysis showed that the positive correlation with GC-enriched bacteria increased, and the positive correlation with GC-depleted bacteria decreased compared to healthy individuals. Functional analyses indicated that pathways related to carbohydrate metabolism were significantly enriched in GC, while biosynthesis of unsaturated fatty acids was diminished. Additionally, we investigated non-Helicobacter pylori (HP) commensals, which are crucial in both HP-negative and HP-positive GC. Random forest models, constructed using specific taxa associated with GC identified from the LEfSe analysis, revealed that the combination of Lactobacillus and Streptococcus included alone could effectively discriminate between GC patients and healthy individuals in fecal samples (area under the curve (AUC) = 0.7949). This finding was also validated in an independent cohort (AUC = 0.7712). Conclusions: This study examined the intratumoral and fecal microbiota of GC patients from a dual microecological perspective and identified Lactobacillus, Streptococcus, Roseburia, Faecalibacterium and Phascolarctobacterium as intratumoral and intestinal-specific co-differential bacteria. Furthermore, it confirmed the validity of the combination of Lactobacillus and Streptococcus as GC-specific microbial markers across multiple populations, which may aid in the early non-invasive diagnosis of GC.

Mucosal microbiota characterization in gastric cancer identifies immune-activated-related transcripts relevant gastric microbiome signatures.

Tumor microenvironment (TME) immune cells and gastric mucosal microbiome constitute two vital elements of tumor tissue. Increasing evidence has elucidated their clinicopathological significance in predicting outcomes and therapeutic efficacy. However, comprehensive characterization of immune cell-associated microbiome signatures in the TME is still in the early stages of development. Here, we characterized the gastric mucosa microbiome and its associations with immune-activated related transcripts (IATs) in 170 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and quantitative reverse transcription-PCR. Microbial diversity and richness were significantly higher in GC tumor tissues than in non-tumor tissues. Differences in microbial composition between the groups were evident, with Firmicutes, Proteobacteria, Bacteroidota, Campilobacterota, Actinobacteria, Fusobacteriota, Verrucomicrobiota, Acidobacteriota, and Cyanobacteria being the dominant phyla in the gastric mucosal microbiota. Microbial interaction network analysis revealed distinctive centralities of oral bacteria (such as Fusobacterium, Porphyromonas, Prevotella, etc.) in both tumor and normal mucosae networks, suggesting their significant influence on GC microbial ecology. Furthermore, we analyzed the expression of IATs (CXCL9, CXCL10, GZMA, GZMB, PRF1, CD8A, IFNG, TBX2, and TNF) and characterized IAT-relevant gastric microbiome signatures in GC patients. Our results showed that the expression of CXCL9, CXCL10, GZMA, GZMB, PRF1 and IFNG was significantly higher in tumor tissues than in adjacent normal tissues in GC patients. Notably, high expression of IATs in tumor tissues was associated with improved survival in GC patients and could serve as a powerful predictor for disease-free survival. Additionally, analysis of IAT levels and mucosal microbiota diversity revealed a correlation between higher IAT expression and increased microbiota richness and evenness in the IATs high group, suggesting potential interactions between mucosal microbiota and tumor immunopathology. Spearman correlation analysis showed positive associations between IAT expression and specific mucosal bacterial species. Notably, Akkermansia muciniphila demonstrated potential involvement in modulating GZMB expression in the GC mucosal microenvironment. These findings underscore the importance of mucosal microbiota alterations in GC and suggest potential therapeutic targets focusing on modulating the tumor microbiota for improved clinical outcomes. The detailed characterization of these elements has profound implications for both treatment and survival prediction in GC. We observed that microbial diversity and richness were significantly higher in GC tumor tissues compared to non-tumor tissues. These differences highlight the unique microbial landscape of GC tumors and suggest that the microbiome could influence tumor development and progression. Importantly, our study demonstrated that high expression levels of IATs in GC tumor tissues were associated with improved patient survival. This suggests that IATs not only reflect immune activation but also serve as valuable biomarkers for predicting disease-free survival. The potential of IATs as predictive markers underscores their utility in guiding therapeutic strategies and personalizing treatment approaches. Moreover, the correlation between higher IAT expression and increased microbiota richness and evenness suggests that a diverse and balanced microbiome may enhance immune responses and contribute to better clinical outcomes. These findings highlight the critical need to consider mucosal microbiota alterations in GC management. Targeting the tumor microbiota could emerge as a promising therapeutic strategy, potentially leading to more effective treatments and improved patient outcomes. Understanding and modulating the microbiome's role in GC opens new avenues for innovative therapeutic interventions and personalized medicine.

Association of Soy Foods With Gastric Cancer Considering Helicobacter pylori: A Multi-Center Case-Control Study.

PURPOSE: This study aims to explore the relationship between soy food consumption and gastric cancer (GC) risk, accounting for Helicobacter pylori infection status. MATERIALS AND METHODS: We analyzed data from patients with GC and healthy individuals prospectively enrolled by 6 hospitals between 2016 and 2018. Dietary intake was evaluated using questionnaires that categorized seven dietary habits and 19 food groups. Multivariate logistic regression models were applied to examine associations. Model I adjusted for various epidemiological factors, while Model II included further adjustments for H. pylori infection. Primary exposures examined were consumption frequencies of nonfermented, unsalted soy foods (soybean/tofu) and fermented, salty soy foods (soybean paste stew). RESULTS: A total of 5,535 participants were included, with 1,629 diagnosed with GC. In Model I, the frequency of soybean/tofu consumption was inversely related to GC risk; adjusted odd ratios (aORs) were 0.62 (95% confidence interval [CI], 0.48-0.8), 0.38 (95% CI, 0.3-0.49), 0.42 (95% CI, 0.33-0.53), and 0.33 (95% CI, 0.27-0.42) for 1 time/week, 2 times/week, 3 times/week, and ≥4 times/week. Consumption of 2 servings/week of soybean paste stew showed the lowest GC association, forming a V-shaped curve. Both low (aOR, 4.03; 95% CI, 3.09-5.26) and high serving frequencies of soybean paste stew (aOR, 2.23; 95% CI, 1.76-2.82) were associated with GC. The association between soy foods and GC in Model II was similar to that in Model I. The soy food-GC associations were consistent across sexes in Model I. Nonetheless, the positive correlation between frequent consumption of soybean paste stew (≥5 times/week) and GC was more pronounced in women (aOR, 7.58; 95% CI, 3.20-17.99) compared to men (aOR, 3.03; 95% CI, 1.61-5.88) in Model II. Subgroup analyses by H. pylori status and salty diet revealed a consistent inverse relationship between soybean/tofu and GC risk. In contrast, soybean paste stew showed a V-shaped relationship in H. pylori-positive or salty diet groups and no significant association in the H. pylori-negative group. CONCLUSIONS: Soybean/tofu intake is consistently associated with a decreased risk of GC. However, the relationship between soybean paste stew consumption and GC risk varies, depending on H. pylori infection status and dietary salt intake. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03046745.

Acute gastroenteritis caused by Vibrio cholerae O1 Ogawa serotype in gastric cancer patient in Eastern India: Case report and review of literature.

ABSTRACT: Acute gastroenteritis is the most common clinical manifestation of Vibrio cholerae infection. Cases of non-O1 V. cholerae infections in cancer patients have been previously reported in the literature. To our best knowledge, this is a unique case of V. cholerae classical biotype, serovar Ogawa infection in a young female patient with gastric malignancy.

Fusobacterium nucleatum: Unraveling its potential role in gastric carcinogenesis.

Fusobacterium nucleatum (F. nucleatum) is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation, such as periodontitis and gingivitis. In the last 10 years, F. nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression, metastasis and poor disease outcome. While the role of F. nucleatum in colon carcinogenesis has been intensively studied, its role in gastric carcinogenesis is still poorly understood. Although Helicobacter pylori infection has historically been recognized as the strongest risk factor for the development of gastric cancer (GC), with recent advances in DNA sequencing technology, other members of the gastric microbial community, and F. nucleatum in particular, have received increasing attention. In this review, we summarize the existing knowledge on the involvement of F. nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F. nucleatum in GC.

Weitiao No. 3 (3) enhances the efficacy of anti-programmed cell death protein-1 immunotherapy by modulating the intestinal microbiota in an orthotopic model of gastric cancer mice.

OBJECTIVE: To explore the effects of Weitiao No. 3 (3, WD-3) on anti-programmed cell death protein-1 (PD-1) immunotherapy in gastric cancer (GC). METHODS: The intestinal microbiota was analyzed by 16S rDNA sequencing of fecal samples from three groups: healthy people (Health), GC patients (GC), and WD-3-treated GC patients (WD-3). Next, we established an orthotopic model of GC mice, which were treated with anti-PD-1, WD-3, or an inoculation of intestinal bacteria. Immune markers CD3, CD4, CD8, and forkhead box protein P3 (FOXP3), and the cell proliferation marker Ki67, were evaluated by immunohistochemistry. Cell apoptosis in GC tumors was assessed by terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling staining. Enzyme-linked immunosorbent assays (ELISAs) were performed to analyze the serum levels of the following cytokines in GC mice: tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-10, interferon (IFN)-γ, and transforming growth factor (TGF)-ß. RESULTS: Sequencing data showed that there were significant differences in the composition of the gut microbial community among the three human groups. The gut bacteria in the three groups mainly comprised the phyla Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. At the genus level, the relative abundances of Bifidobacterium and Coprococcus showed significant decreases in the GC group, and an obvious increase in the WD-3 group, compared with the Health group. Interestingly, the relative abundance of Saccharopolyspora was only detected in the WD-3 group. The results of in vivo experiments in GC mice showed that WD-3 or anti-PD-1 treatment increased the levels of CD3+, CD4+, and CD8+ T cells, but decreased the levels of FOXP3+ regulatory T cells. Furthermore, WD-3 or PD-1 antibody treatment inhibited proliferation and promoted apoptosis of GC tumor cells. ELISA analysis showed that WD-3 or PD-1 antibody treatment facilitated TNF-α, IL-2, and IFN-γ expression, while suppressing IL-6, IL-10, and TGF-ß expression. Combination therapy with WD-3 and anti-PD-1 intensified all of these effects. CONCLUSION: WD-3 enhanced the immunotherapeutic efficacy of anti-PD-1 by modulating the intestinal microbiota in an orthotopic model of GC mice.

Association of miR-499 rs3746444, miR-149 rs2292832 polymorphisms and their expression levels with helicobacter pylori-related gastric diseases and Traditional Chinese Medicine syndromes.

OBJECTIVE: To provide an objective experimental basis for the gastric mucosa pathological evolution and the transformation of different Traditional Chinese Medicine (TCM) syndromes in helicobacter pylori (H. pylori)-related gastric diseases (HPGD) patients, based on the combination of TCM syndrome differentiation, molecular biology and histopathology. METHODS: A total of 203 participants were enrolled in this study. The expressions of miR-499/miR-149 and H. pylori infection in the gastric tissues from all participants were detected. The genotyping for miR-499 rs3746444 and miR-149 rs2292832 was performed. RESULTS: In H. pylori positive subjects, the proportion of precancerous gastric lesions (PGL) in liver-stomach disharmony syndrome (LSDS) group was higher than in spleen Qi deficiency syndrome (SQDS) group (P <0.001); The proportion of gastric cancer (GC) in SQDS group was higher than in spleen-stomach damp-heat syndrome (SSDHS) group and LSDS group (all P <0.001). We also found C allele of miR-149 rs2292832 was linked to lower risk of gastric atrophy [miR-149 rs2292832 C vs T: adjusted odds ratio = 0.207; 95% confidence interval (0.043-0.989); P = 0.048]. Compared with healthy control (HC) group, the expression of miR-499 was significantly increased in GC group, while the expression of miR-149 was significantly decreased in chronic inflammation group, PGL group and GC group (all P < 0.05). Test for trend showed that GC risk was on a rising trend with the increasing expression of miR-499 and decreasing expression of miR-149 (both P for trend < 0.05). CONCLUSION: The C allele of miR-149 rs2292832 may be a protective factor for gastric mucosal atrophy. H. pylori may participate in the evolution of benign to malignant gastric mucosa lesions by inducing the overexpression of miR-499 and down regulation of miR-149. In addition, patients with H. pylori infection combined SQDS or LSDS may have higher risk of gastric mucosal malignant lesions.

Impact of Helicobacter pylori on immunotherapy in gastric cancer.

This study reviews the contrasting finding regarding the impact of Helicobacter pylori infection on the efficacy of immunotherapy in gastric cancer (GC). While a large retrospective study reported a positive association between H. pylori infection and progression-free survival (PFS)/overall survival (OS) in patients with GC undergoing PD-1/PD-L1 therapy, previous studies had given rise to a contrary outcome. Potential explanations of the inconsistency include the divergent immune responses induced by different H. pylori status (current infection, postinfection and negative status) directly, as well as the indirect influence of gut microbiota alterations. Tumor molecular subtypes, particularly Epstein-Barr virus (EBV) infection status, may also play a role in the discrepancy by altering the profile of immune infiltration. However, data on EBV status are absent in studies showing H. pylori infection as an unfavorable factor for GC immunotherapy. Moreover, a combined positive score (CPS) <1 might exert a positive influence, as more patients with CPS<1 enrolled in the study reported a positive association between H. pylori infection and immunotherapy. The review highlights the need for further research to clarify the complex interplay between H. pylori infection, immune response, and immunotherapy efficacy in GC, aiming to develop more targeted and personalized treatment strategies.

Helicobacter pylori induce circ_0046854 to regulate microRNA-511-3p/CSF1 axis and enhance the resistance of gastric cancer to cisplatin.

Helicobacter pylori (HP) is considered a major risk factor for gastric cancer (GC) and during this process, cytotoxin­associated gene A (CagA) plays in essence. The study mainly focused on the molecular mechanism of circular RNA 0046854 (circ_0046854) in HP-induced GC. Clinically, 56 cases of GC and normal tissues were collected, and the GC tissues were divided into HP-negative GC tissues (HP-) and 33 HP-positive GC tissues (HP+). Tissue expression of circ_0046854, microRNA (miR)-511-3p and colony-stimulating factor 1 (CSF1) was tested. BGC-823/Cisplatin (DDP) resistant strain was induced and cell growth and DDP resistance were detected after HP infection. In vivo experiments were performed using a mouse xenograft model. The relationship between circ_0046854, miR-511-3p and CSF1 was confirmed. GC tissues especially HP+ cancer tissues expressed high circ_0046854 and CSF1 and low miR-511-3p. HP-induced circ_0046854 expression in GC cells through CagA. Inhibition of circ_0046854 or miR-511-3p elevation inhibited the growth and DDP resistance in GC cells. Circ_0046854 acted as a sponge for miR-511-3p, which targeted CSF1. Restoring CSF1 could abolish the inhibitory effect of miR-511-3p overexpression on CagA+ HP-induced GC progression in vitro. Circ_0046854 silencing repressed tumor growth and aggrandized the inhibiting effects of DDP on tumorigenesis in vivo. Circ_0046854/miR-511-3p/CSF1 axis may be involved in the development of HP-induced GC, thus providing new ideas for studying the mechanism of HP-related gastric diseases.

Regulation of cagA-Helicobacter on gastric PIM2 expression in gastric cancer.

BACKGROUND: The association between infection with cagA-positive H. pylori and an elevated susceptibility to gastric cancer has been firmly established. PIM2 is known to be overexpressed in various types of cancers; however, the specific mechanism by which cagA influences the regulation of PIM2 expression in gastric cancer remains unidentified at present. MATERIALS AND METHODS: A mutant NCTC11637ΔcagA strain of H. pylori and the eukaryotic expression vector pcDNA-cagA were constructed for evaluating PIM2 expression levels in gastric cancer cells (HGC27, SGC7901, and AG) co-cultured with the NCTC11637 and NCTC11637ΔcagA strain, as well as pcDNA-cagA and the empty vector pcDNA3.1 (+). RESULTS: Co-culturing gastric cancer cells with NCTC11637 significantly increased PIM2 expression levels (P< 0.001) compared to the negative control group. Additionally, the expression of PIM2 in cells co-cultured with NCTC11637 was higher than that co-cultured with NCTC11637ΔcagA (P< 0.001). Furthermore, successful construction of the eukaryotic expression vector pcDNA-cagA resulted in a significant increase in PIM2 mRNA expression levels after its transfection into gastric cancer cells compared to the control group after 48 hours. CONCLUSIONS: The findings indicate that H. pylori/cagA A could be one of the key factors in regulating PIM2 expression levels, potentially influencing the progression of H. pylori-related Gastric Cancer.

Identification of shared and disease-specific intratumoral microbiome-host gene associations in gastrointestinal tumors.

Intratumoral microbiota and host genes interact to promote gastrointestinal disorders, but how the two interact to influence host tumorigenesis remains unclear. Here, we utilized a machine learning-based framework to jointly dissect the paired intratumoral microbiome and host transcriptome profiles in patients with colon adenocarcinoma, hepatocellular carcinoma, and gastric cancer. We identified associations between intratumoral microbes and host genes that depict shared as well as cancer type-specific patterns. We found that a common set of host genes and pathways implicated in cell proliferation and energy metabolism are associated with cancer type-specific intratumoral microbes. In addition, we also found that intratumoral microbes that have been implicated in three gastrointestinal tumors, such as Lachnoclostridium, are correlated with different host pathways in each tumor, indicating that similar microbes can influence host tumorigenesis in a cancer type-specific manner by regulation of different host genes. Our study reveals patterns of association between intratumoral microbiota and host genes in gastrointestinal tumors, providing new insights into the biology of gastrointestinal tumors.NEW & NOTEWORTHY Our study constitutes a pivotal advancement in elucidating the intricate relationship between the intratumoral microbiome and host gene regulation, thereby gaining insights into the pivotal role that the intratumoral microbiome plays in the etiology of gastrointestinal tumors.

Effectiveness of long-term low-dose aspirin in the prevention of gastric cancer after Helicobacter pylori eradication: study design and rationale of Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT).

BACKGROUND: In addition to Helicobacter pylori (H. pylori) infection eradication, some medications, including aspirin, metformin, and statins, have been suggested to have protective effects against gastric cancer (GC) development in observational studies. We launched the Ardabil gastric cancer randomized placebo-controlled prevention trial (AGCPT) to evaluate the effectiveness of long-term low-dose aspirin use for the prevention of development and mortality of GC after H. pylori eradication. METHODS/DESIGN: AGCPT is a prospective population-based double-blind, randomized clinical trial. The study sample was targeted at 21,000 participants aged from 35 to 70 years old, both sexes, in Ardabil, a province in northwest Iran with relatively high rates of GC incidence and mortality. All eligible participants were initially tested for H. pylori infection using a H. pylori stool antigen test. Participants with positive tests undergo H. pylori eradication by standard treatment regimens. All participants with a negative test and those with a positive test with a subsequent confirmed H. pylori eradication test were entered into the intervention phase. In the intervention phase, participants were allocated randomly into either the treatment (daily oral consumption of 81 mg enteric-coated aspirin tablets) arm or the control (placebo) arm using permuted balanced blocks. Subjects will be followed for an average period of 10 years to evaluate the incidence and mortality rates of GC. DISCUSSION: In addition to preventing other diseases like cardiovascular events, aspirin may prevent GC incidence and mortality. AGCPT will investigate the difference between the two study arms in the proportion of the cumulative incidence and mortality rates of GC. The study's results may help policymakers and researchers update the strategies for GC prevention. TRIAL REGISTRATION: This trial with the registry name of "The effect of Low-dose Aspirin in the Prevention of Gastric Cancer" was registered in the Iranian Registry of Clinical Trials, IRCT.ir, under the identifier IRCT201105082032N3. Registered on April 21, 2017.

Increasing our knowledge about the epidemiology of Helicobacter pylori in Nunavik's Inuit population (Québec, Canada) using Qanuilirpitaa? 2017 cross-sectional survey.

Helicobacter pylori is a bacterium that may colonise and proliferate in human stomachs, leading invariably to chronic inflammation and, to a lesser extent, to peptic ulcers and cancer. The main objective of this study is to describe the epidemiology surrounding H. pylori in Nunavik's Inuit population using the 2004 and 2017 Health Surveys. Estimated prevalences were 70.9% for bacterial colonisation using a stool antigens test (SAT), 72.5% for anti-H. pylori antibodies, 12.7% for faecal occult blood in participants aged ≥ 50 and respectively of 28.4%, 11.2% and 2.4% for a prior diagnosis of colonisation, gastritis and peptic ulcer in the medical charts, with under five cases of gastric cancer reported. Variables associated with higher SAT+ prevalence were the number of household members (prevalence ratio [PR] = 1.03) and age (quadratic relationship), whereas mainly drinking municipal (PR = 0.84) and natural water (PR = 0.72) compared to bottled water, and increasing alcohol consumption (PR = 0.96) were associated with reduced prevalence. Despite current regional guidelines targeting high risk individuals in the context of high prevalence, Nunavik's health authorities must remain vigilant by following gastric cancer incidence and the rapid evolution of guidelines, while considering local realities.

Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.

Background: The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Methods: Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. Results: The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. Conclusion: The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.

Helicobacter pylori CagA mediated mitophagy to attenuate the NLRP3 inflammasome activation and enhance the survival of infected cells.

Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease.

Virulence gene polymorphisms in Shandong Helicobacter pylori strains and their relevance to gastric cancer.

BACKGROUND: Helicobacter pylori (H. pylori) virulence factors, particularly the cagA and vacA genotypes, play important roles in the pathogenic process of gastrointestinal disease. METHODS: The cagA and vacA genotypes of 87 H. pylori strains were determined by PCR and sequencing. The EPIYA and CM motif patterns were analyzed and related to clinical outcomes. We examined the associations between the virulence genes of H. pylori and gastrointestinal diseases in Shandong, and the results were analyzed via the chi-square test and logistic regression model. RESULTS: Overall, 76 (87.36%) of the strains carried the East Asian-type CagA, with the ABD types being the most prevalent (90.79%). However, no significant differences were observed among the different clinical outcomes. The analysis of CagA sequence types revealed 8 distinct types, encompassing 250 EPIYA motifs, including 4 types of EPIYA or EPIYA-like sequences. Additionally, 28 CM motifs were identified, with the most prevalent patterns being E (66.67%), D (16.09%), and W-W (5.75%). Notably, a significant association was discovered between strains with GC and the CM motif pattern D (P < 0.01). With respect to the vacA genotypes, the strains were identified as s1, s2, m1, m2, i1, i2, d1, d2, c1, and c2 in 87 (100%), 0 (0), 26 (29.89%), 61 (70.11%), 73 (83.91%), 14 (16.09%), 76 (87.36%), 11 (12.64%), 18 (20.69%), and 69 (79.31%), respectively. Specifically, the vacA m1 and c1 genotypes presented a significantly greater prevalence in strains from GC compared to CG (P < 0.05). Following adjustment for age and sex, the vacA c1 genotype demonstrated a notable association with GC (OR = 5.174; 95% CI, 1.402-20.810; P = 0.012). This association was both independent of and more pronounced than the correlations between vacA m1 and GC. CONCLUSIONS: CagA proteins possessing CM motif pattern D were more frequently observed in patients with GC (P < 0.01), implying a potentially higher virulence of CM motif pattern D than the other CM motif patterns. Moreover, a strong positive association was identified between the vacA c1 genotype and GC, indicating that the vacA c1 genotype is a robust risk indicator for GC among male patients aged ≥55 years in Shandong.

Protocol to establish an accelerated murine model for Helicobacter-induced gastric cancer.

Helicobacter-induced gastric cancer progresses very slowly, even in animal models, making it difficult to study. Here, we present a protocol to establish an accelerated murine model for Helicobacter-induced gastric cancer. We describe steps for infecting mice with Helicobacter felis, harvesting gastric tissue, assessing disease severity by histopathologic scoring, and performing gene expression studies with RT-qPCR and RNA sequencing. The accelerated model shows rapid progression of the disease, with gastric precancerous lesions developing within 6 months post-infection with Helicobacter. For complete details on the use and execution of this protocol, please refer to Bali et al.1.

Impacts of Matrix Metalloproteinase-8 Genotypes, Smoking, Alcohol Drinking, and Helicobacter Pylori Infection on Gastric Cancer.

BACKGROUND/AIM: In gastric cancer (GCa) tissues, mRNA expression of matrix metalloproteinase-8 (MMP-8) is notably reduced compared to healthy tissues. Furthermore, abnormally low or elevated serum levels of MMP-8 have been linked to a significantly poor prognosis. The involvement of MMP-8 genotypes in susceptibility to GCa remains underexplored. We aimed to assess the influence of MMP-8 genotypes on GCa susceptibility and their potential interactions with smoking, alcohol consumption, and Helicobacter pylori (H. pylori) infection. PATIENTS AND METHODS: The study utilized polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) to analyze MMP-8 rs11225395, rs34009635, and rs35866072 genotypes in 161 GCa patients and 483 controls. RESULTS: No statistically significant difference was detected in the distribution of genotypic (p for trend=0.3635) or allelic (p=0.1954) frequencies of MMP-8 rs11225395. Under a dominant model, combined CT+TT genotypes showed no association with GCa risk [odds ratio (OR)=0.77, 95% confidence interval (95%CI)=0.54-1.10, p=0.1852]. Similarly, no association was observed for MMP-8 rs34009635 or rs35866072. Importantly, individuals with the MMP-8 rs11225395 CC genotype demonstrated a significant increase in GCa risk when exposed to smoking (OR=4.04, 95%CI=2.28-7.16, p=0.0001), alcohol consumption (OR=2.83, 95%CI=1.64-4.89, p=0.0002), and H. pylori infection (OR=3.53, 95%CI=2.12-5.90, p=0.0001). CONCLUSION: The findings indicate that individuals carrying the MMP-8 rs11225395 CC genotype have increased susceptibility to GCa, especially when combined with risk factors, such as smoking, alcohol consumption, and H. pylori infection. These results suggest that MMP-8 genotype-based preventive strategies, including lifestyle alterations and targeted infection treatments, may be valuable in mitigating GCa development.