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Turkish Journal of Medical Sciences 2023The common disease gastric adenocarcinoma (GAC) has a high morbidity and mortality, so there is an urgent need for research to explore new diagnostic markers and...
BACKGROUND/AIM
The common disease gastric adenocarcinoma (GAC) has a high morbidity and mortality, so there is an urgent need for research to explore new diagnostic markers and therapeutic targets. This investigation was carried out to investigate the expression of sphingomyelin phosphodiesterase acid-like 3b (SMPDL3B) in GAC and its effects on tumor progression.
MATERIALS AND METHODS
Samples were collected from patients who underwent radical gastrectomy from January 2021 to December 2022. Along with the normal gastric epithelial cell lines GES-1 and SGC-7901, the AGS, MGC-803, and MSN-45 human gastric cancer cell lines were used to confirm SMPDL3B expression. RT-qPCR, Western blot, immunohistochemical, cell proliferation, assay of wound healing, transwell migration assay, invasion assay, flow cytometry, and immune evaluation experiments were carried out.
RESULTS
SMPDL3B was found to be substantially expressed in GAC, and this condition has a bad prognosis. By establishing SMPDL3B knockdown and overexpression of GAC cell lines, this study confirmed that SMPDL3B promoted tumor cell proliferation, migration, and invasion. Additional bioinformatics research revealed a connection between SMPDL3B and immune cell infiltration in the GAC immunological microenvironment, which enhanced tumor cell proliferation by promoting the infiltration content of M2 macrophages.
CONCLUSION
This study determined the function of SMPDL3B for the clinical diagnosis, prediction, and novel management of GAC.
Topics: Humans; Stomach Neoplasms; Adenocarcinoma; Cell Proliferation; Cell Line, Tumor; Macrophages; Cell Movement; Sphingomyelin Phosphodiesterase; Disease Progression; Male; Female; Middle Aged; Tumor Microenvironment
PubMed: 38813495
DOI: 10.55730/1300-0144.5732 -
World Journal of Gastroenterology May 2024Gastric cystica profunda (GCP) is an uncommon but underestimated gastric lesion. Its precancerous potential determines its significance. In addition to previous mucosa...
Gastric cystica profunda (GCP) is an uncommon but underestimated gastric lesion. Its precancerous potential determines its significance. In addition to previous mucosa injury due to operations, biopsy or polypectomy, chronic active and atrophic gastritis may also lead to the development of GCPs. By carefully examining the stomach and taking biopsy samples from the susceptible regions, the stage of atrophy can be determined. Chronic atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs formation. GCPs frequently occur close to early gastric cancers (EGCs) or EGC can arise from the cystic glands. Endoscopic resection is an effective and minimally invasive treatment in GCP.
Topics: Humans; Biopsy; Chronic Disease; Cysts; Gastric Mucosa; Gastritis, Atrophic; Gastroscopy; Precancerous Conditions; Risk Factors; Stomach Diseases; Stomach Neoplasms
PubMed: 38813049
DOI: 10.3748/wjg.v30.i17.2308 -
Frontiers in Immunology 2024Chondroitin sulfate synthase 3 (CHSY3) is an important enzyme that regulates glycosylation, but its role in tumors has not been determined. Here, we showed that high...
Chondroitin sulfate synthase 3 (CHSY3) is an important enzyme that regulates glycosylation, but its role in tumors has not been determined. Here, we showed that high CHSY3 expression promotes proliferation in gastric cancer (GC) cells and is associated with poor prognosis in GC patients. We analyzed the immunohistochemistry data of 150 gastric cancer patients to determine the clinicopathological and survival significance of CHSY3. Immunofluorescence was used to detect the colocalization of CHSY3 with infiltrating immune cells. Additionally, CHSY3 was predominantly found in tumor tissues and showed higher abundance compared to matched adjacent tissues. High CHSY3 expression was associated with more advanced tumor stage, higher recurrence risk and worse survival. Immunohistochemistry and bioinformatic analysis revealed that CHSY3 expression was significantly positively correlated with tumor-associated macrophage (TAM) infiltration. Moreover, after knocking down CHSY3, the proliferation of cells was decreased, and the migration ability was reduced, as shown by scratch, monoclonal and transwell assays. In conclusion, this study revealed that CHSY3 has a tumor-promoting effect on GC, suggesting a novel therapeutic strategy against this disease.
Topics: Humans; Stomach Neoplasms; Prognosis; Female; Male; Cell Proliferation; Middle Aged; Cell Line, Tumor; Cell Movement; Biomarkers, Tumor; Tumor-Associated Macrophages; Aged; Gene Expression Regulation, Neoplastic
PubMed: 38812506
DOI: 10.3389/fimmu.2024.1364979 -
Frontiers in Bioscience (Landmark... May 2024Gastric cancer (GC) is frequently diagnosed at advanced stages, when cancer cells have already metastasized. Therefore, patients with GC have a low survival rate and...
BACKGROUND
Gastric cancer (GC) is frequently diagnosed at advanced stages, when cancer cells have already metastasized. Therefore, patients with GC have a low survival rate and poor prognosis even after treatment.
METHODS
We downloaded GC-related RNA sequencing (RNA-Seq) data, copy number variation (CNV) data, and clinical data for bioinformatics analysis to screen prognostic genes of GC. Single-sample gene set enrichment analysis and survival analyses were performed on the RNA-Seq data, and differential and correlation analyses were conducted on the CNV data to obtain CNV-driven differentially expressed genes (DEGs). Prognostic genes were identified through univariate Cox analyses of the CNV-driven DEGs, combined with the clinical data. () was finally selected for verification after functional and survival analyses of the prognostic genes.
RESULTS
expression was lower in paracancer tissue than in GC tissue, and lower in GES-1 gastric epithelial cells than in GC cells. The cell culture supernatants from -knockdown GC cells were collected and used to culture human umbilical vein endothelial cells (HUVECs). It was observed that enhanced the activity, metastasis, invasion, and angiogenesis of GC cells; promoted the epithelial-mesenchymal transition (EMT) of GC cells; and impacted the Ras-associated protein 1 (Rap1)/mitogen-activated protein kinase (MAPK) pathway. To further explore the involvement of the Rap1/MAPK pathway in GC development, a pathway activator was added to GC cells with knockdown of expression. This pathway activator not only enhanced the activity, invasion, and migration of GC cells but also promoted the EMT and blood vessel formation.
CONCLUSIONS
regulates the angiogenesis and EMT of GC cells through the Rap1/MAPK pathway, thus influencing the onset and progression of GC.
Topics: Stomach Neoplasms; Humans; Epithelial-Mesenchymal Transition; Neovascularization, Pathologic; Cell Line, Tumor; Prognosis; Gene Expression Regulation, Neoplastic; MAP Kinase Signaling System; Human Umbilical Vein Endothelial Cells; Shelterin Complex; Male; Female; Telomere-Binding Proteins; DNA Copy Number Variations; Cell Movement; rap1 GTP-Binding Proteins; Angiogenesis
PubMed: 38812308
DOI: 10.31083/j.fbl2905177 -
Frontiers in Bioscience (Landmark... May 2024Gastric adenocarcinoma (GAC) is a malignant tumor with the highest incidence in the digestive system. Macrophages have been proven to play important roles in tumor...
BACKGROUND
Gastric adenocarcinoma (GAC) is a malignant tumor with the highest incidence in the digestive system. Macrophages have been proven to play important roles in tumor microenvironment.
METHODS
Herein, single-cell RNA sequencing (scRNA-seq) profiles from the Gene Expression Omnibus (GEO) and bulk RNA-seq data from the Cancer Genome Atlas (TCGA) database were utilized to construct a macrophage marker gene signature (MMGS) to predict the prognosis of GAC patients. Subsequently, a risk score model based on the MMGS was built to predict the prognosis of GAC patients; further, this was validated in the GEO cohort. The risk score categorized patients into the high- and low-risk groups. A nomogram model based on the risk score and clinic-pathological characteristics was developed.
RESULTS
Seven genes, , , , , , , and , were included in the risk score model. Patients with a low-risk score showed a better prognosis. The MMGS had good sensitivity and specificity for predicting the prognosis inGAC patients. The risk score was an independent prognostic factor. The constructed nomogram exhibited favorable predictability and reliability for predicting GAC prognosis.
CONCLUSION
In conclusion, the risk score model based on the seven MMGSs performed well in the predicting prognosis of GAC patients. Our study may provide new insights into clinical decision-making for the personalized treatment of patients with gastric cancer (GC).
Topics: Humans; Stomach Neoplasms; Prognosis; Adenocarcinoma; Computational Biology; Biomarkers, Tumor; Nomograms; Male; Female; Gene Expression Regulation, Neoplastic; Macrophages; Tumor Microenvironment; Middle Aged; Transcriptome; Gene Expression Profiling; Aged
PubMed: 38812299
DOI: 10.31083/j.fbl2905172 -
World Journal of Surgical Oncology May 2024The applicability of laparoscopy to nonmetastatic T4a patients with gastric cancer remains unclear due to the lack of high-quality evidence. The purpose of this study... (Meta-Analysis)
Meta-Analysis Comparative Study
Laparoscopic versus open gastrectomy for nonmetastatic T4a gastric cancer: a meta-analysis of reconstructed individual participant data from propensity score-matched studies.
BACKGROUND
The applicability of laparoscopy to nonmetastatic T4a patients with gastric cancer remains unclear due to the lack of high-quality evidence. The purpose of this study was to compare the survival rates of laparoscopic gastrectomy (LG) versus open gastrectomy (OG) for these patients through a meta-analysis of reconstructed individual participant data from propensity score-matched studies.
METHODS
PubMed, Embase, Web of Science, Cochrane library and CNKI were examined for relevant studies without language restrictions through July 25, 2023. Individual participant data on overall survival (OS) and disease-free survival (DFS) were extracted from the published Kaplan-Meier survival curves. One-stage and two-stage meta-analyses were performed. In addition, data regarding surgical outcomes and recurrence patterns were also collected, which were meta-analyzed using traditional aggregated data.
RESULTS
Six studies comprising 1860 patients were included for analysis. In the one-stage meta-analyses, the results demonstrated that LG was associated with a significantly better DFS (Random-effects model: P = 0.027; Restricted mean survival time [RMST] up to 5 years: P = 0.033) and a comparable OS (Random-effects model: P = 0.135; RMST up to 5 years: P = 0.053) than OG for T4a gastric cancer patients. Two-stage meta-analyses resulted in similar results, with a 13% reduced hazard of cancer-related death (P = 0.04) and 10% reduced hazard of overall mortality (P = 0.11) in the LG group. For secondary outcomes, the pooled results showed an association of LG with less estimated blood loss, faster postoperative recovery and more retrieved lymph nodes.
CONCLUSION
Laparoscopic surgery for patients with nonmetastatic T4a disease is associated with a potential survival benefit and improved surgical outcomes.
Topics: Stomach Neoplasms; Humans; Gastrectomy; Laparoscopy; Propensity Score; Survival Rate; Prognosis; Neoplasm Staging
PubMed: 38812025
DOI: 10.1186/s12957-024-03422-5 -
Epidemiology and Health May 2024Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract...
OBJECTIVES
Mercury can stimulate immune responses through T helper 17 (Th17). The gene IL23R is a key factor in Th17 function, which may also contribute to digestive tract diseases. The aim of this study was to observe the associations between dietary mercury and gastric cancer (GC) and to investigate whether the IL23R rs10889677 polymorphism modifies those associations.
METHODS
This case-control study included 377 patients with GC and 756 healthy controls. Dietary mercury intake (total mercury and methylmercury) was assessed using a dietary heavy metal database incorporated into the food frequency questionnaire. IL23R genetic polymorphism rs10889677 (A>C) was genotyped. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression models with adjustments for potential confounders.
RESULTS
A higher dietary methylmercury intake was associated with an elevated risk of GC (OR for the highest versus lowest tertile [T3 vs. T1]=2.02; 95% CI, 1.41-2.91; p for trend <0.001). The IL23R rs10889677 reduced the risk of GC in individuals who carried at least 1 minor allele (OR=0.62; 95% CI, 0.46-0.83; p=0.001; AC/CC vs. AA). Individuals with a C allele exhibited a lower susceptibility to GC through methylmercury intake than those with the AA genotype (OR for the T3 of methylmercury and AA carriers=2.93; 95% CI, 1.77-4.87; and OR for the T3 of methylmercury and AC/CC genotype=1.30; 95% CI, 0.76-2.21; p-interaction=0.013).
CONCLUSION
Our findings suggest that a genetic polymorphism, rs10889677 in IL23R, plays a role in modifying the association between dietary methylmercury intake and the risk of GC.
PubMed: 38810984
DOI: 10.4178/epih.e2024051 -
Endoscopy Dec 2024
Topics: Humans; Stomach Neoplasms; Endoscopic Mucosal Resection; Male; Adenocarcinoma; Gastric Mucosa; Aged; Female; Middle Aged
PubMed: 38810978
DOI: 10.1055/a-2321-9626 -
JAMA Network Open May 2024Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic...
IMPORTANCE
Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown.
OBJECTIVE
To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu.
EXPOSURES
H pylori treatment and nutrition supplementation.
MAIN OUTCOMES AND MEASURES
Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk.
RESULTS
Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.
Topics: Humans; Stomach Neoplasms; Female; Male; Middle Aged; Helicobacter pylori; Helicobacter Infections; Genetic Predisposition to Disease; China; Genome-Wide Association Study; Case-Control Studies; Adult; Risk Factors; Dietary Supplements; Cohort Studies; Aged; Anti-Bacterial Agents
PubMed: 38809553
DOI: 10.1001/jamanetworkopen.2024.13708 -
Frontiers in Immunology 2024Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical...
BACKGROUND
Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body's anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors.
METHODS
Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments.
RESULTS
GC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of was distributed in endothelial cells. Cellular experiments demonstrated that facilitated the proliferation of GC cells.
CONCLUSION
This is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.
Topics: Humans; Stomach Neoplasms; Manganese; Prognosis; Tumor Microenvironment; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Transcriptome; Gene Expression Profiling; Immunotherapy; Male; Female; Databases, Genetic
PubMed: 38807601
DOI: 10.3389/fimmu.2024.1377472