Development Of Gastric Cancer Research Articles

Hereditary Gastric Cancer Is Linked With Hereditary Breast and Ovarian Cancer.

Helicobacter pylori (H. pylori), a bacterium which chronically infects the stomach of approximately half the world's population, is a risk factor for the development of gastric cancer (GC). However, the underlying mechanism whereby H. pylori infection induces GC development remains unclear. Intermittent injection of the H. pylori cytotoxin-associated gene A antigen (CagA) protein into its host cell inhibits nuclear translocation of BRCA1/BRCA2, DNA repair proteins involved in the development of breast cancer/ovarian cancer. Interestingly, hereditary breast and ovarian cancer (HBOC) syndrome is associated with GC development. Here, we aimed to clarify the molecular link between H. pylori infection, BRCA1/2 pathogenic variants (PVs), GC and higher GC incidence in HBOC families. We retrospectively reviewed data from Japanese patients undergoing precision treatment using cancer genomic medicine. We found a higher GC incidence in HBOC families having germline pathogenic variants (GPVs) of BRCA1/2 (2.95% vs. 0.78% in non-HBOC families). Next, we found that 96.1% of H. pylori-infected patients received cancer genomic medicine for advanced GC, and > 16% advanced GC patients had gBRCA2 PVs. Furthermore, expressing wild-type BRCA1/2 in Gan mice (a mouse model of human GC) inhibited GC development. Thus, gBRAC1/2 PVs and H. pylori infection synergistically increase the risk of GC development. Our study highlights the need to investigate the potential of therapeutic agents against BRCA1/2 PVs to avoid the development of GC in HBOC families. In addition, our results suggest that poly (ADP-ribose) polymerase (PARP) inhibitors could potentially inhibit GC development and progression with gBRCA1/2 PVs.

Programmed cell death in Helicobacter pylori infection and related gastric cancer

Programmed cell death (PCD) plays a crucial role in maintaining the normal structure and function of the digestive tract in the body. Infection with Helicobacter pylori (H. pylori) is an important factor leading to gastric damage, promoting the Correa cascade and accelerating the transition from gastritis to gastric cancer. Recent research has shown that several PCD signaling pathways are abnormally activated during H. pylori infection, and the dysfunction of PCD is thought to contribute to the development of gastric cancer and interfere with treatment. With the deepening of studies on H. pylori infection in terms of PCD, exploring the interaction mechanisms between H. pylori and the body in different PCD pathways may become an important research direction for the future treatment of H. pylori infection and H. pylori-related gastric cancer. In addition, biologically active compounds that can inhibit or induce PCD may serve as key elements for the treatment of this disease. In this review, we briefly describe the process of PCD, discuss the interaction between different PCD signaling pathways and the mechanisms of H. pylori infection or H. pylori-related gastric cancer, and summarize the active molecules that may play a therapeutic role in each PCD pathway during this process, with the expectation of providing a more comprehensive understanding of the role of PCD in H. pylori infection.

CircRHBDD1 promotes immune escape via IGF2BP2/PD-L1 signaling and acts as a nanotherapeutic target in gastric cancer

BackgroundCircular RNAs (circRNAs) have been implicated in the development and progression of gastric cancer (GC). However, it remains unclear whether dysregulated circRNA affects immune escape and the efficacy of immunotherapy in GC. Our aim is to investigate the molecular mechanism of circRNA affecting GC immunotherapy and identify effective molecular therapeutic targets.MethodsThe differential expression profile of circRNAs was established through circRNA sequencing, comparing three paired GC tissues with their adjacent non-cancerous gastric tissues. The expression level of circRHBDD1 in GC tissues was then assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The biological characteristics of circRHBDD1 were verified through a series of experiments, including agarose gel electrophoresis assays, RNase R treatment, and actinomycin D experiments. The prognostic value of circRHBDD1 in GC was evaluated by conducting both univariate and multivariate survival analyses. Furthermore, loss- and gain-of-function approaches were utilized to investigate the impact of circRHBDD1 on GC immune escape. RNA-sequencing, immunoprecipitation, flow cytometry, and methylated RNA immunoprecipitation (meRIP) analysis were performed to elucidate the underlying molecular mechanisms.ResultsWe discovered that circRHBDD1 exhibited remarkably high expression levels in GC tissues and cell lines. Notably, the high expression of circRHBDD1 was significantly correlated with poor overall survival and disease-free survival among GC patients. Both in vitro and in vivo experiments revealed that circRHBDD1 upregulated the expression of PD-L1 and impeded the infiltration of CD8+ T cells. Further, we found that circRHBDD1 binds to IGF2BP2, disrupting the interaction between E3 ligase TRIM25 and IGF2BP2, and ultimately inhibiting IGF2BP2 ubiquitination and degradation. Intriguingly, IGF2BP2 enhances PD-L1 mRNA stability through m6A modification. Additionally, we developed Poly (lactide-co-glycolic acid) (PLGA)-Polyethylene glycol (PEG)-based nanoparticles loaded with circRHBDD1 siRNA. In vivo experiments validated that the combination of PLGA-PEG(si-circRHBDD1) and anti-PD-1 offers a safe and efficacious nano-drug regimen for cancer immunotherapy.ConclusionOur results demonstrated that circRHBDD1 promoted GC immune escape by upregulating the expression of PD-L1 and reprogramming T cell-mediated immune response. Inhibition of circRHBDD1 expression could potentially enhance the response of GC patients to immunotherapy, thus improving treatment outcomes. Additionally, the development of a nanodrug delivery system provides a feasible approach for future clinical applications.

Modern approaches to diagnosing and preventing malignization of peptic ulcer in the practice of the general practitioner from the perspective of evidence-based medicine

Background: Peptic ulcer disease (PUD) is a prevalent gastrointestinal disorder that affects millions globally and has the potential to transform into gastric cancer (GC). GC ranks as the fifth most common cancer and is notably lethal. A significant correlation exists between PUD and Helicobacter pylori infection, which disrupts the stomach lining, leading to ulcers that may become malignant if not properly managed. Methods and Materials: This study employed a systematic analysis and meta-analysis approach, gathering data from multiple medical databases including Medscape, Medline, Scopus, Pubmed, and various gastrointestinal guidelines from regions such as Malaysia, Europe, and the United States. The primary methods involved comparing the risk of malignization between gastric and duodenal ulcers, assessing the sensitivity of different diagnostic methods, and determining optimal prevention strategies. Results: The findings indicate that gastric ulcers have a higher risk of malignization compared to duodenal ulcers. Diagnostic methods such as endoscopic biopsy demonstrated higher sensitivity for early malignization detection. Screening programs, especially those targeting H. pylori eradication, significantly reduce the incidence and mortality rates associated with gastric cancer. Conclusion: Early diagnosis and prevention of PUD malignization are vital for improving patient outcomes. Effective strategies include the use of sensitive diagnostic methods and comprehensive screening programs for H. pylori. Lifestyle modifications and vigilant monitoring by healthcare professionals are also crucial in reducing the risk of peptic ulcer malignization and subsequent gastric cancer development.

The Impact of Tobacco Smoking and Alcohol Consumption on the Development of Gastric Cancers.

Chronic infection of Helicobacter pylori is considered the principal cause of gastric cancers, but evidence has accumulated regarding the impact of tobacco smoking and alcohol consumption on the development of gastric cancers. Several possible mechanisms, including the activation of nicotinic acetylcholine receptors, have been proposed for smoking-induced gastric carcinogenesis. On the other hand, local acetaldehyde exposure and ethanol-induced mucosal inflammation have been proposed as the mechanisms involved in the development of gastric cancers in heavy alcohol drinkers. In addition, genetic polymorphisms are also considered to play a pivotal role in smoking-related and alcohol-related gastric carcinogenesis. In this review, we will discuss the molecular mechanisms involved in the development of gastric cancers in relation to tobacco smoking and alcohol consumption.

Association between serum total cholesterol and the development of gastric cancer: A two-way two-sample Mendelian randomization study.

Previous epidemiologic studies have suggested a potential negative correlation between total cholesterol (TC) and Gastric cancer (GC); however, several observational studies have shown conflicting results and have failed to provide definitive evidence for a causal relationship between TC and GC. Therefore, we conducted a 2-sample bidirectional Mendelian randomization (MR) study to explore the genetic correlation and potential causal relationship between the 2 variables. We screened for single nucleotide polymorphisms (SNPs) associated with TC and GC utilizing a large-scale genome-wide association study (GWAS) public database. The causal relationship was analyzed using 5 MR analysis methods: inverse variance weighting (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. Additionally, reverse MR analysis was performed to evaluate the possibility of reverse causality. Sensitivity analyses were conducted, including heterogeneity tests, horizontal multiple validity tests, and leave-one-out tests. After meticulous screening, 79 SNPs were identified as instrumental variables (IVs). The IVW method revealed a causal relationship between TC and GC (OR = 0.844; 95% CI: 0.741-0.961; P = .01). Sensitivity analyses did not detect significant horizontal pleiotropy. Though heterogeneity was observed in the forward MR analysis (IVW, Qp = 0.0006), the results remained reliable as we utilized the IVW random-effects model as the primary analytical method. Furthermore, inverse MR analysis found no evidence of reverse causality between TC and GC, effectively ruling out the influence of GC on the reverse causality of TC. Our MR study provided evidence of a causal association between TC and GC, suggesting that TC acts as a protective factor against GC due to its negative association with the disease.

Streptococcus anginosus: A new pathogenof superficial gastritis, atrophic gastritisand gastric cancer.

A wealth of research indicates that superficial gastritis (SG) and atrophic gastritis (AG) are precursors to gastric cancer (GC). While Helicobacter pylori (H. pylori) has long been recognized as a key player in GC development, recent findings by Fu et al. have identified Streptococcus anginosus (S. anginosus) as an emerging pathogen that can trigger SG, AG and GC. S. anginosus, a gram-positive coccus, leverages its surface protein T. pallidum membrane protein C (TMPC) to engage with the annexin A2 (ANXA2) receptor of gastric epithelial cells, facilitating its colonization and invasion in the gastric mucosa. This leads to an upregulation of proinflammatory chemokines Ccl20 and Ccl8, causing prolonged effects on gastric barrier function and microbiota homeostasis, leading to SG. Moreover, these bacteria activate the mitogen-activated protein kinase (MAPK) signaling pathway, which is associated with the development of AG and GC. Importantly, inhibiting TMPC or knocking down ANXA2 can reduce S. anginosus colonization and invasion, lowering the chances of SG, AG, and GC. This paper highlights the molecular mechanisms of S. anginosus in SG, AG and GC, emphasizing the importance of a multi-pathogen strategy in gastric disease management and the need for further investigation into the role of S. anginosus in GC progression.

The role of reactive oxygen species in gastric cancer.

Gastric cancer (GC) ranks fifth in cancer incidence and fourth in cancer-related mortality worldwide. Reactive oxygen species (ROS) are highly oxidative oxygen-derived products that have crucial roles in cell signaling regulation and maintaining internal balance. ROS are closely associated with the occurrence, development, and treatment of GC. This review summarizes recent findings on the sources of ROS and the bidirectional regulatory effects on GC and discusses various treatment modalities for GC that are related to ROS induction. In addition, the regulation of ROS by natural small molecule compounds with the highest potential for development and applications in anti-GC research is summarized. The aim of the review is to accelerate the clinical application of modulating ROS levels as a therapeutic strategy for GC.

The role of reactive oxygen species in gastric cancer.

Gastric cancer (GC) ranks fifth in cancer incidence and fourth in cancer-related mortality worldwide. Reactive oxygen species (ROS) are highly oxidative oxygen-derived products that have crucial roles in cell signaling regulation and maintaining internal balance. ROS are closely associated with the occurrence, development, and treatment of GC. This review summarizes recent findings on the sources of ROS and the bidirectional regulatory effects on GC and discusses various treatment modalities for GC that are related to ROS induction. In addition, the regulation of ROS by natural small molecule compounds with the highest potential for development and applications in anti-GC research is summarized. The aim of the review is to accelerate the clinical application of modulating ROS levels as a therapeutic strategy for GC.

Comprehensive multiomics analysis of the signatures of gastric mucosal bacteria and plasma metabolites across different stomach microhabitats in the development of gastric cancer.

As an important component of the microenvironment, the gastric microbiota and its metabolites are associated with tumour occurrence, progression, and metastasis. However, the relationship between the gastric microbiota and the development of gastric cancer is unclear. The present study investigated the role of the gastric mucosa microbiome and metabolites as aetiological factors in gastric carcinogenesis. Gastric biopsies from different stomach microhabitats (n = 70) were subjected to 16S rRNA gene sequencing, and blood samples (n = 95) were subjected to untargeted metabolome (gas chromatography‒mass spectrometry, GC‒MS) analyses. The datasets were analysed using various bioinformatics approaches. The microbiota diversity and community composition markedly changed during gastric carcinogenesis. High Helicobacter. pylori colonization modified the overall diversity and composition of the microbiota associated with gastritis and cancer in the stomach. Most importantly, analysis of the functional features of the microbiota revealed that nitrate reductase genes were significantly enriched in the tumoral microbiota, while urease-producing genes were significantly enriched in the microbiota of H. pylori-positive patients. A panel of 81 metabolites was constructed to discriminate gastric cancer patients from gastritis patients, and a panel of 15 metabolites was constructed to discriminate H. pylori-positive patients from H. pylori-negative patients. receiver operator characteristic (ROC) curve analysis identified a series of gastric microbes and plasma metabolites as potential biomarkers of gastric cancer. The present study identified a series of signatures that may play important roles in gastric carcinogenesis and have the potential to be used as biomarkers for diagnosis and for the surveillance of gastric cancer patients with minimal invasiveness.

Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway

Long noncoding RNAs (lncRNAs) serve as critical mediators of tumor progression and drug resistance in cancer. Herein, we identified a lncRNA, LINC00665, associated with trastuzumab resistance and development in gastric cancer (GC). LINC00665 was highly expressed in GC tissues and high expression of LINC00665 was correlated with poor prognosis. LINC00665 knockdown was verified to suppress migration, invasion, and resistance to trastuzumab in GC. Furthermore, we found that LINC00665 participates in the infiltration of naive B cells, mast cells, and T follicular helper (Tfh) cells. Mechanistically, LINC00665 was confirmed to regulate tumorigenesis and trastuzumab resistance by activating PI3K/AKt pathway. LINC00665 sponged miR-199b-5p to interact with SERPINE1 expression, resulting in the increase of phosphorylation of AKt, thus participating in the PI3K/AKt pathway. To summarize, LINC00665 facilitated the tumorigenesis and trastuzumab resistance of GC by sponging miR-199b-5p and promoting SERPINE1 expression, which further activated PI3K/AKt signaling; this finding reveals a new mechanism by which LINC00665 modulates tumor development and drug resistance in GC.

The role of dysregulated metabolism and associated genes in gastric cancer initiation and development

The role of dysregulated metabolism and associated genes in gastric cancer initiation and development

ARID1A is involved in DNA double-strand break repair in gastric cancer.

Defects in DNA damage repair can cause genetic mutations, which in turn can cause different types of cancers. Chromatin remodeling complexes, which help repair damaged DNA, can cause the chromatin structure to change as a result of DNA damage. ARID1A may play a role in the process of DNA damage repair, and arid1a may be related to the occurrence and development of gastric cancer (GC). This study aimed to investigate the mechanism of ARID1A regulating the DNA damage repair of gastric adenocarcinoma cell lines AGS and SGC-7901 and its effect on migration, proliferation and apoptosis. The expression of ARID1A plasmid was detected by Western blot and real-time polymerase chain reaction (PCR). The effect of etoposide (ETO) on the survival rate of AGS and SGC-7901 gastric adenocarcinoma cell lines was detected by MTT assay. The DNA double-strand break model was established by ETO and then passed through the comet assay and immunofluorescence co-localization to observe DNA damage; western blot method was used to detect the effect of ARID1A on the expression of related proteins in DNA damage repair pathway in gastric adenocarcinoma cells; scratch test and colony formation experiments were used to observe ARID1A migration and proliferation of gastric adenocarcinoma cells. The flow cytometry was used to detect the effect of ARID1A on apoptosis of gastric adenocarcinoma cells. The expression of mRNA and protein was increased after transfection of ARID1A plasmid. ETO was confirmed by MTT assay to inhibit cell survival in a dose-dependent manner. After the DNA double-strand break model was established by ETO, the expression levels of phospho-ataxia telangiectasia mutated (p-ATM) protein increased in the overexpressed ARID1A group. Meanwhile, the overexpressed ARID1A group had a shortened tail moment, and γ-H2AX and ARID1A co-localized in the DNA damage site of the nucleus. The over-expressed ARID1A group had weaker wound healing ability, reduced number of clone formation, and increased apoptosis rate. ARID1A may repair DNA double-strand breaks caused by ETO by p-ATM pathway; ARID1A can inhibit the migration and proliferation of gastric adenocarcinoma cells and promote apoptosis. Our findings indicate that ARID1A could serve as a therapeutic target and biomarker for GC patients.

Proteomic Characterization of a Lunasin-Enriched Soybean Extract Potentially Useful in the Treatment of Helicobacter pylori Infection.

Helicobacter pylori infection affects over 50% of the world's population and leads to chronic inflammation and gastric disorders, being the main pathogen correlated to gastric cancer development. Increasing antibiotic resistance levels are a major global concern and alternative treatments are needed. Soybean peptides and other compounds might be an alternative in the treatment to avoid, eradicate and/or control symptoms of H. pylori infection. This study aimed to characterize a lunasin-enriched soybean extract (LSE) using proteomics tools and to evaluate its antioxidant, anti-inflammatory and antibacterial properties against H. pylori infection. By LC-MS/MS analysis, 124 proteins were identified, with 2S albumin (lunasin and large-chain subunits) being the fourth most abundant protein (8.9%). Lunasin consists of 44 amino acid residues and an intramolecular disulfide bond. LSE at a low dose (0.0625 mg/mL) reduced ROS production in both H. pylori-infected and non-infected AGS gastric cells. This led to a significant reduction of 6.71% in the levels of pro-inflammatory interleukin (IL)-8. LSE also showed antibacterial activity against H. pylori, which can be attributed to other soybean proteins and phenolic compounds. Our findings suggest that LSE might be a promising alternative in the management of H. pylori infection and its associated symptoms.

Ferroptosis regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer.

Gastric cancer is one of the most common malignant tumors in the world, and its occurrence and development involve complex biological processes. Iron death, as a new cell death mode, has attracted wide attention in recent years. However, the regulatory mechanism of iron death in gastric cancer and its effect on lipid peroxidation metabolism remain unclear. To explore the role of iron death in the development of gastric cancer, reveal its relationship with lipid peroxidation, and provide a new theoretical basis for revealing the molecular mechanism of the occurrence and development of gastric cancer. The process of iron death in gastric cancer cells was simulated by cell culture model, and the occurrence of iron death was detected by fluorescence microscopy and flow cytometry. The changes of gene expression related to iron death and lipid peroxidation metabolism were analyzed by high-throughput sequencing technology. In addition, a mouse model of gastric cancer was established, and the role of iron death in vivo was studied by histology and immunohistochemistry, and the level of lipid peroxidation was detected. These methods comprehensively and deeply reveal the regulatory mechanism of iron death on lipid peroxidation metabolism in the occurrence and development of gastric cancer. Iron death was significantly activated in gastric cancer cells, and at the same time, associated lipid peroxidation levels increased significantly. Through high-throughput sequencing analysis, it was found that iron death regulated the expression of several genes related to lipid metabolism. In vivo experiments demonstrated that increased iron death in gastric cancer mice was accompanied by a significant increase in lipid peroxidation. This study confirmed the important role of iron death in regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer. The activation of iron death significantly increased lipid peroxidation levels, revealing its regulatory mechanism inside the cell.

OLFM4 promotes the progression of intestinal metaplasia through activation of the MYH9/GSK3β/β-catenin pathway

BackgroundIntestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression.MethodsIn this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM.ResultsOur results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3β and resulted in increased β-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells.ConclusionsOLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.

Pachyman alleviates cognitive impairment after sevoflurane anesthesia in gastric cancer surgery

Cancer cell metastasis has already taken place in most of the gastric cancer (GC) patients when diagnosed. Despite that surgery effectively delays the development of GC, sevoflurane anesthetic during surgery tends to cause cognitive impairment. Previous studies have depicted anti-tumor and neuroprotective effects of pachyman. Therefore, this study aimed at investigating a potential mechanism whereby pachyman alleviates cognitive impairment after sevoflurane anesthesia in GC surgery. A rat model of GC was constructed and received treatment with pachyman at different concentrations and caspase-3 inhibitor and agonist. After treatment, the level of inflammatory factors was detected by ELISA. Flow cytometer and Morris water maze were conducted to assess cell death and cognitive function, followed by HE gastric histopathological staining. In addition, RT-qPCR and Western blot detected GSH-PX and caspase-3 expression. Pachyman positively induced the apoptosis of GC cells and strengthened the cognitive function of rats with downregulated caspase-3. Moreover, caspase-3 inhibitor also accelerated apoptosis and improved rat cognitive function. When caspase-3 was inhibited, the level of GSH-PX was elevated. Combination of pachyman and caspase-3 inhibitor more significantly induced GC cell apoptosis and alleviated cognitive impairment. Pachyman alleviates the cognitive impairment caused by sevoflurane anesthesia in GC rats and induces tumor cell apoptosis through down-regulation of caspase-3 and up-regulation of GSH-PX.

An Immunoinformatic Approach to Designing a Multi-Epitope Vaccine against Helicobacter pylori with the VacA Toxin and BabA Adhesion

Objective: Helicobacter pylori, as a carcinogen, has been related to the development of gastric cancer, particularly in developing countries. The main challenge with therapy is the recurrence of antibiotic-resistant bacteria, and vaccination is still a problem. Therefore, the objective of the current study was to rationally design a multi-epitope vaccine using two immunogenic proteins found in H. pylori. Methods: Promising epitopes for the Leb-binding adhesin A (BabA) and vacuolating cytotoxin (VacA) proteins were characterized through an immunoinformatics approach. Epitope-rich fragments were selected based on high-binding affinities with HLA classes I and II to be specifically presented to B and T lymphocytes and to selectively elicit both humoral and cellular immune responses. Results: Six constructs were planned by fusing these fragments in different arrangements with the help of GPGPG linkers. The most stable three-dimensional structure was found in Construct 6 during molecular dynamics. To improve immunogenicity and stability, an adjuvant called human β- defensin 2 (hBD-2) was joined to the N-terminus of Construct 6. Following molecular docking, the final vaccine reacted appropriately with each toll-like receptor 2 (TLR-2), TLR3, and TLR-4. The final DNA sequence was optimized for expression in E. coli K12 and in silico cloned into a pET-28a(+) plasmid. As a result of the vaccination in silico, substantial responses were developed against H. pylori. Conclusion: According to the immune response simulation, activated B and T lymphocytes and memory cell production increased. Macrophages and dendritic cells proliferated continuously, and IFN-γ and Cytokines, such as IL-2 were raised.

Clinical implications and mechanism of CST1 in gastric carcinoma based on database screening.

Gastric cancer (GC) remains one of the most common malignant tumours worldwide, with extremely high morbidity and mortality rates. An in-depth understanding of the pathogenesis of GC is key to the future diagnosis and treatment of GC. In this study, we analysed the differentially expressed genes (DEGs) in gastric carcinoma (GC) through GEO database and their clinical implications, with the aim of providing clinical reference and guidance. We selected the GSE118916 dataset for bioinformatics analysis and identified a total of 3231 DEGs. Keywords, including extracellular region, vesicle, protein digestion and absorption, ECM-receptor interaction, etc., of DEGs can be seen by the GO and KEGG enrichment analysis. The online database determined up-regulated CST1 in GC and some other tumors, as well as a close connection between CST1 with patient prognosis. Subsequently, we collected a number of GC clinical cases and examined the expression of CST1, which was seen to be highly expressed in GC, with a favorable diagnostic effect on the occurrence of GC (P<0.05) and a strong correlation with TNM stage, tumor invasion, tumor diameter and differentiation (P<0.05). In other words, CST1 is closely related to the occurrence and development of GC, and has the potential to be a breakthrough in the diagnosis and treatment of GC in the future.

Possible Role of Cytomegalovirus in Gastric Cancer Development and Recurrent Macrolide-Resistant Campylobacter jejuni Infection in Common Variable Immunodeficiency: A Case Report and Literature Discussion.

Common variable immunodeficiency (CVID) is the most common symptomatic immunodeficiency in adults. It comprises a group of syndromes whose etiology involves genetic, epigenetic, microbiota, and environmental factors. We present the case of a 46-year-old Caucasian male patient with CVID and an immune dysregulation phenotype. The particular elements of the case consisted of an atypical clinical course, which undoubtedly demonstrates the great variability of clinical manifestations that these types of patients can suffer from, including bacterial and viral infections, autoimmune phenomena, and neoplasia. Notably, the patient suffered from recurrent gastrointestinal infection with macrolide-resistant Campylobacter jejuni and gastroduodenal disease and viraemia by cytomegalovirus (CMV). In addition, CMV was postulated as the main pro-oncogenic factor contributing to the development of early-onset intestinal-type gastric adenocarcinoma, for which the patient underwent gastrectomy. The patient's evolution was difficult, but finally, as a result of the multidisciplinary approach, clinical stabilization and improvement in his quality of life were achieved. Based on our brief literature review, this is the first reported case of this clinical complexity. Our experience could help with the management of future patients with CVID and may also update current epidemiological data on CVID.