Gastric Cancer Mortality Research Articles

GDF15 enhances anoikis resistance and metastasis of gastric cancer through protective autophagy

Distant metastasis is a prevalent cause of mortality in gastric cancer (GC) patients. Anoikis, a process that induces cell death when cells get detached from the extracellular matrix (ECM), acts as a barrier to tumor metastasis. To survive in the circulatory system and metastasize, tumor cells must acquire anoikis resistance. It is crucial to identify the molecular processes that cause resistance to anoikis in GC since this might lead to the discovery of novel treatment targets and improve the long-term survival of GC patients. In this study, we employed quantitative proteomics to identify growth differentiation factor 15 (GDF15) as a key factor in GC anoikis resistance. We found that GDF15 enhances protective autophagy, thereby promoting anoikis resistance in GC cells. Furthermore, through DNA pull down assay, activating transcription factor 2 (ATF2) was found to be a critical regulator of GDF15 expression, acting as a transcriptional activator of GDF15. Collectively, these discoveries indicate that ATF2 and GDF15 have great potential as target candidates for developing therapeutic strategies to address the metastasis of GC.

Cost-Effectiveness of Serum Pepsinogen as a Gastric Cancer Targeted Screening Strategy in the United States

Background and AimsCurrent gastric cancer (GC) screening modalities are invasive and expensive. Noninvasive screening for GC precursors with serum pepsinogen (PG) may improve early detection and prevention. Test characteristics of PG based on US prospective data was recently reported and used to study the cost-effectiveness of PG screening versus no screening in the US. MethodsA patient-level state transition microsimulation of gastric adenocarcinoma analyzed noninvasive screening versus no screening in a hypothetical cohort of average risk US individuals. Primary outcomes included life expectancy, quality-adjusted life years (QALYs), total costs, and incremental cost-effectiveness ratios (ICERs). Secondary outcomes included total GC incidence and mortality. Base-case PG sensitivity and specificity were 34.1% and 94.7%, respectively, with a wide range of PG performance characteristics also examined. ResultsOne-time serum PG screening at age 40 was cost-effective compared to no screening with an ICER of $4,913.29 per QALY. PG screening resulted in 10.9% relative reduction in lifetime GC incidence and 10.8% relative decrease in cumulative GC mortality. Localized stage at diagnosis increased from 30.5% to 33.6% and metastatic stage decreased from 40.8% to 37.4%. Sensitivity analysis showed PG screening was most sensitive to endoscopy costs, chronic atrophic gastritis quality of life, and PG prevalence. PG screening remained cost-effective across a wide range of test values. ConclusionPG screening is a cost-effective strategy to improve GC mortality, however, mortality benefit will depend on the test characteristics of the biomarker. Future blood-based screening tests that have better performance characteristics could further improve GC prevention.

S2330 Racial/Ethnic Disparities in Gastric Cancer Incidence and Mortality Among Individuals Aged 50 Years and Above: A Population-Based Analysis

S2330 Racial/Ethnic Disparities in Gastric Cancer Incidence and Mortality Among Individuals Aged 50 Years and Above: A Population-Based Analysis

Screening for Helicobacter pylori to Prevent Gastric Cancer

Effects of screening for Helicobacter pylori on gastric cancer incidence and mortality are unknown. To evaluate the effects of an invitation to screen for H pylori on gastric cancer incidence and mortality. A pragmatic randomized clinical trial of residents aged 50 to 69 years in Changhua County, Taiwan, eligible for biennial fecal immunochemical tests (FIT) for colon cancer screening. Participants were randomized to either an invitation for H pylori stool antigen (HPSA) + FIT assessment or FIT alone. The study was conducted between January 1, 2014, and September 27, 2018. Final follow-up occurred December 31, 2020. Invitation for testing for H pylori stool antigen. The primary outcomes were gastric cancer incidence and gastric cancer mortality. All invited individuals were analyzed according to the groups to which they were randomized. Of 240 000 randomized adults (mean age, 58.1 years [SD, 5.6]; 46.8% female), 63 508 were invited for HPSA + FIT, and 88 995 were invited for FIT alone. Of the 240 000 randomized, 38 792 who were unreachable and 48 705 who did not receive an invitation were excluded. Of those invited, screening participation rates were 49.6% (31 497/63 508) for HPSA + FIT and 35.7% (31 777/88 995) for FIT alone. Among 12 142 participants (38.5%) with positive HPSA results, 8664 (71.4%) received antibiotic treatment, and eradication occurred in 91.9%. Gastric cancer incidence rates were 0.032% in the HPSA + FIT group and 0.037% in the FIT-alone group (mean difference, -0.005% [95% CI, -0.013% to 0.003%]; P = .23). Gastric cancer mortality rates were 0.015% in the HPSA + FIT group and 0.013% in the FIT-alone group (mean difference, 0.002% [95% CI, -0.004% to 0.007%]; P = .57). After adjusting for differences in screening participation, length of follow-up, and patient characteristics in post hoc analyses, an invitation for HPSA + FIT was associated with lower rates of gastric cancer (0.79 [95% CI, 0.63-0.98]) but not with gastric cancer mortality (1.02 [95% CI, 0.73-1.40]), compared with FIT alone. Among participants who received antibiotics, the most common adverse effects were abdominal pain or diarrhea (2.1%) and dyspepsia or poor appetite (0.8%). Among residents of Taiwan, an invitation to test for HPSA combined with FIT did not reduce rates of gastric cancer or gastric cancer mortality, compared with an invitation for FIT alone. However, when differences in screening participation and length of follow-up were accounted for, gastric cancer incidence, but not gastric cancer mortality, was lower in the HSPA + FIT group, compared with FIT alone. ClinicalTrials.gov Identifier: NCT01741363.

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)

BackgroundIn 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/designAGCPT 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.DiscussionIn 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 registrationThis 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.

The Naples Score: Can it Outperform Existing Scores in Predicting Gastric Cancer Mortality?

Objective: Gastric surgery, including curative and palliative procedures, is crucial in managing gastric cancer. Despite advancements, postoperative mortality remains a significant concern, influenced by factors such as patient nutritional status. Accurate assessment of nutritional status is essential for risk stratification and improving patient outcomes.This study aims to investigate the correlation between four nutritional scores: Naples Prognostic Score , Controlling Nutritional Status score, Prognostic Nutritional Index, and Systemic Inflammation Score and the mortality rate following gastric surgery, to identify the most reliable predictors of postoperative mortality. Materials and methods: This retrospective study evaluated 50 patients diagnosed with gastric adenocarcinoma and operated on at Erol Olçok Training and Research Hospital between April 2021 and September 2023. Data collected included age, gender, operation type, laparoscopy usage, albumin, cholesterol, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, mortality rates, and TNM stages. Nutritional scores were calculated, and their predictive accuracy for mortality was assessed using time-dependent Receiver Operating Characteristic curve analysis. Results: The study included 50 patients. Significant differences in albumin levels, neutrophil-to-lymphocyte rate, lymphocyte-to-monocyte ratio, and nutritional scores were found between deceased and surviving patients. Prognostic Nutritional Index had the highest predictive accuracy with an Area under the curve of 0.792, sensitivity of 76%, and specificity of 86.2%, outperforming others. Conclusion: The Prognostic Nutritional Index is the most effective predictor of postoperative mortality among the evaluated scores.

Trends of older gastric cancer incidence, mortality, and survival in the highest gastric cancer risk area in China: 2010–2019 and prediction to 2024

BackgroundGastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024.MethodsThe study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi’s world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024.ResultsBased on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77–4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5–63.2%) in 2010 to 34.4% (95%CI, 32.1–36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5–55.1%) in 2010 to 34.2% (95%CI, 32.0–36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024.ConclusionFrom 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years.

Metal contamination of the surface water and its effect on the higher gastric cancer incidence of Lujiang County, China

Metal contamination in surface water is one of the major environmental risk factors contributing to the incidence and mortality of gastric cancer (GC) in rural China. In this study, the generalized additive model (GAM) was used to explore the single and interactive effects of metal elements in surface water on GC incidence on the watershed scale in Lujiang County, east of China. Spatially, the areas with a high incidence of GC were concentrated in the northwest watershed where the drainage system was relatively developed. Apart from Sr, the average concentrations of Al, As, Be, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Sn, and Zn in the northern watershed were higher than those in the southern watershed. Among them, the average concentrations of Be (0.036 mg/L), Fe (1.539 mg/L), Mn (0.355 mg/L), and Ni (0.040 mg/L) well exceeded China’s Grade III water quality standards. On the sub-watershed scale Be (F(5.130)), Pb (F(4.963)), As (F(3.508)), Cu (F(3.023)), Zn (F(2.922)), Cr (F(2.725)), Sn (F(2.588)), and Co (F(2.140)) in surface water were the main elements contributing to the high incidence of GC in Lujiang County, and the interaction effect mostly showed nonlinear enhancement. Especially, the nonlinear enhancement effect of Be with Cu (F(7.051)), Co (F(5.798)), Sn (F(5.328)), and Pb (F(5.193)) was more significant and had a greater effect on the incidence of GC. This study provides compelling direct evidence on the effects of metal contamination in surface water on the higher GC incidence in Lujiang County, China. It is recommended that there be routine monitoring of metal concentrations in surface water resources.

Postoperative body weight change and its influencing factors in patients with gastric cancer.

The high incidence and mortality of gastric cancer (GC) pose a significant threat to human life and health, and it has become an important public health challenge in China. Body weight loss is a common complication after surgical treatment in patients with GC and is associated with poor prognosis and GC recurrence. However, current attention to postoperative weight change in GC patients remains insufficient, and the descriptions of postoperative weight change and its influencing factors are also different. To investigate body weight changes in patients with GC within 6 mo after gastrectomy and identify factors that influence dynamic body weight changes. We conducted a prospective longitudinal study of 121 patients with GC and collected data before (T0) and 1 (T1), 3 (T2), and 6 (T3) mo after gastrectomy using a general data questionnaire, psychological distress thermometer, and body weight measurements. The general estimation equation (GEE) was used to analyze the dynamic trends of body weight changes and factors that influence body weight changes in patients with GC within 6 mo of gastrectomy. The median weight loss at T1, T2, and T3 was 7.29% (2.84%, 9.40%), 11.11% (7.64%, 14.91%), and 14.75% (8.80%, 19.84%), respectively. The GEE results showed that preoperative body mass index (BMI), significant psychological distress, religious beliefs, and sex were risk factors for weight loss in patients with GC within 6 mo after gastrectomy (P < 0.05). Compared with preoperative low-weight patients, preoperative obese patients were more likely to have weight loss (β = 14.685, P < 0.001). Furthermore, patients with significant psychological distress were more likely to lose weight than those without (β = 2.490, P < 0.001), and religious patients were less likely to lose weight 6 mo after gastrectomy than those without religious beliefs (β = -6.844, P = 0.001). Compared to female patients, male patients were more likely to experience weight loss 6 mo after gastrectomy (β = 4.262, P = 0.038). Male patients with GC with high preoperative BMI, significant psychological distress, and no religious beliefs are more likely to lose weight after gastrectomy.

High Gastric Cancer Mortality and Years of Life Lost in Nicaragua: A Population-Based Study 1997 - 2012.

Gastric adenocarcinoma (GC) is the fourth leading cause of cancer-related mortality, and leading infection-associated cancer. GC has striking geographic variability, with high incidence in East Asia and mountainous Latin America. Reliable cancer data and population-based cancer registries (PBCRs) are lacking for the majority of LMICs, including the Central American Four region (CA-4, Nicaragua, El Salvador, Honduras, and Guatemala). Mortality data for Nicaragua were obtained from the highly-rated Ministry of Health death registry. All the patients were diagnosed with gastric cancer between 1997 and 2012 (ICD-10 codes C16.0-C16.9) and death due to any cause were included in the study. Data on variables such as sex, age (stratified by 5-year age groups), municipality, urban/rural, altitude, and year of death were analyzed. A total of 3,886 stomach cancer deaths were reported in Nicaragua between 1997 and 2012, of which 2,214 (56.9%) were male. The ASMR were 13.1 and 8.7 per 100,000 habitants for males and females, respectively, and without significant change during the study period (APC= -0.7, P=0.2). An average of 17.9 years were lost per death (AYLL), accounting for 67,964 years of life lost (YYL). The burden of gastric cancer mortality is high in Nicaragua with significantly elevated ASMR, YYL, and AYLL. The projected increase in mortality portends the double cancer burden in northern Central America, with persistent infection-associated cancers and growing transition cancers (e.g., breast and colon cancers), which has implications for cancer control in Mesoamerica and U.S. Latino populations.

Curcumin Induces Autophagy-mediated Ferroptosis by Targeting the PI3K/AKT/mTOR Signaling Pathway in Gastric Cancer.

As a very common malignancy of the digestive system, the incidence and mortality rates of gastric cancer (GC) are increasing year by year. The critical role of ferroptosis in cancer development has been well-documented. The polyphenol compound curcumin shows prominent anti-tumor effects in multiple cancer types, including GC. However, whether curcumin participates in GC tumorigenesis by regulating ferroptosis remains unknown. Gastric cancer cells AGS and HGC-27 were treated with curcumin (0, 10, and 20 μM). Cell viability and death were evaluated through CCK-8 and LDH release assays. LC3B expression in cells was estimated through immunofluorescence staining. Intracellular ferrous iron (Fe2+), GSH, MDA, and lipid ROS levels were assessed by corresponding assay kits. The cellular levels of autophagy markers (ATG5, ATG7, Beclin 1, and LC3B), ferroptosis markers (ACSL4, SLC7A11, and GPX4), and phosphorylated (p)-PI3K, p-AKT, and p-mTOR were determined through western blotting. Curcumin attenuated cell viability but stimulated cell death in GC cells. Curcumin enhanced autophagy in GC cells, as demonstrated by the increased levels of ATG5, ATG7, Beclin 1, and LC3B. Besides, curcumin upregulated iron, MDA, GSH, and ACSL4 levels while downregulated lipid ROS, SLC7A11, and GPX4 levels, suggesting its stimulation on ferroptosis in GC cells. Curcumin decreased p-PI3K, p-AKT, and p-mTOR levels in cells. Importantly, the ferroptosis inhibitor ferrostatin-1 overturned the impacts of curcumin on GC cell viability, death, and ferroptosis. Curcumin suppresses GC development by inducing autophagy-mediated ferroptosis by inactivating the PI3K/AKT/mTOR signaling.

Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035.

To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth.

Bioinformatics analysis of the association between obesity and gastric cancer.

Obesity and gastric cancer (GC) are prevalent diseases worldwide. In particular, the number of patients with obesity is increasing annually, while the incidence and mortality rates of GC are ranked high. Consequently, these conditions seriously affect the quality of life of individuals. While evidence suggests a strong association between these two conditions, the underlying mechanisms of this comorbidity remain unclear. We obtained the gene expression profiles of GSE94752 and GSE54129 from the Gene Expression Omnibus database. To investigate the associated biological processes, pathway enrichment analyses were conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for the shared differentially expressed genes in obesity and GC. A protein-protein interaction (PPI) network was subsequently established based on the Search Tool for the Retrieval of Interacting Genes (STRING) database, followed by the screening of the core modules and central genes in this network using Cytoscape plug-in MCODE. Furthermore, we scrutinized the co-expression network and the interplay network of transcription factors (TFs), miRNAs, and mRNAs linked to these central genes. Finally, we conducted further analyses using different datasets to validate the significance of the hub genes. A total of 246 shared differentially expressed genes (209 upregulated and 37 downregulated) were selected for ensuing analyses. Functional analysis emphasized the pivotal role of inflammation and immune-associated pathways in these two diseases. Using the Cytoscape plug-in CytoHubba, nine hub genes were identified, namely, CXCR4, CXCL8, CXCL10, IL6, TNF, CCL4, CXCL2, CD4, and CCL2. IL6 and CCL4 were confirmed as the final hub genes through validation using different datasets. The TF-miRNA-mRNA regulatory network showed that the TFs primarily associated with the hub genes included RELA and NFKB1, while the predominantly associated miRNAs included has-miR-195-5p and has-miR-106a-5p. Using bioinformatics methods, we identified two hub genes from the Gene Expression Omnibus datasets for obesity and GC. In addition, we constructed a network of hub genes, TFs, and miRNAs, and identified the major related TFs and miRNAs. These factors may be involved in the common molecular mechanisms of obesity and GC.

Comparing global trends in gastric cancer and the need for national screening programs: An in-depth literature review

Abstract Introduction Gastric cancer, though experiencing a decline in mortality rates, remains a global concern. This study explores the impact of screening strategies and Helicobacter pylori eradication on gastric cancer incidence and mortality, emphasizing global variations in risk factors and screening programs. Methods A literature review was conducted, searching PubMed and Medline databases for relevant studies. Two distinct searches focused on national screening programs and H. pylori eradication effects, yielding 11,378 studies. Selection criteria refined the studies to 37, emphasizing trial data and recent publications. Statistical analysis, including forest plots, was employed to examine screening outcomes and H. pylori eradication therapy. Results Screening demonstrated a 31% decrease in gastric cancer mortality, with varied incidence outcomes. Population control studies showed an insignificant risk reduction (odds ratio [OR] 0.92), while case–control studies indicated an expected increase in cancer incidence (OR 5.15). Screening intervals of 12 months or less correlated with a 30% mortality risk reduction, and repeated screenings further decreased the risk by 79%. H. pylori eradication therapy exhibited a 56% decrease in cancer odds, emphasizing its significance in both asymptomatic and high-risk individuals. Discussion The study underscores the efficacy of screening methods, with endoscopy and Barium X-ray playing pivotal roles in early detection. Optimal screening intervals and the impact of repeated screenings on mortality risk are highlighted. H. pylori eradication emerges as a critical intervention, with a focus on overcoming challenges such as clarithromycin resistance. Successful screening programs in high-risk regions offer insights for global implementation, with research indicating promising avenues for preventive strategies.

The mechanism of RGS5 regulating gastric cancer mismatch repair protein.

The incidence and mortality rates of gastric cancer (GC) remain alarmingly high worldwide, imposing a substantial healthcare burden. In this study, we utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A 4-gene prognostic model was developed to predict patient prognosis, and its accuracy was validated across multiple datasets. Patients with a low-risk score exhibited improved prognosis, elevated tumor mutation burden, heightened sensitivity to both immunotherapy and conventional chemotherapy. Notably, our investigation revealed that the key gene RGS5 positively modulates the expression of mismatch repair proteins via c-Myc. Furthermore, co-immunoprecipitation (COIP) assays demonstrated the interaction between RGS5 and c-Myc. Additionally, we confirmed that RGS5 regulates c-Myc through the ubiquitin-proteasome pathway. Moreover, RGS5 was identified as a positive regulator of PD-L1 expression and exhibited a negative correlation with the majority of immune cells. These findings underscore the potential of RGS5 as a novel biomarker and therapeutic target in the context of GC.

Effect of Age at Diagnosis on the Prognosis of Gastric Cancer Patients: A Population-Based Study in Georgia.

The national burden of gastric cancer (GC) is high in Georgia, which is determined by its high mortality and low survival. The study aimed to estimate the effect of age at diagnosis on the prognosis of GC patients diagnosed between 2015 and 2020 in Georgia. We obtained data for the study from the national population-based cancer registry. All patients 15 years of age or older, diagnosed during 2015-2020 with invasive GC (site codes C16.0 to C16.9, International Classification of Diseases for Oncology), were eligible for inclusion in the analysis. We produced survival curves using the Kaplan-Meier method, and the log-rank test was used to compare survival between groups. Hazard ratios (HR) were estimated using univariate Cox proportional models and multivariate Cox proportional hazard models. The endpoint of the study was overall survival (OS). The level of statistical significance of the study findings was estimated using p-values and 95% confidence intervals (CI). A p-value<0.05 was considered statistically significant. Results: A total of 1,828 gastric cancer cases were included in the statistical analysis. The average age of patients was 65 years. The bivariate Cox's regression analysis demonstrated that the risk of gastric cancer mortality increased gradually with the age of cancer patients. The HR and 95% CI were as follows: 1.5 (1.1-1.8) and 2.1 (1.5-2.5) in the 46-65 years and >65 years groups, respectively, with the <46 years group as a reference. Moreover, multivariable Cox's regression analysis proved that age is an independent risk factor for GC mortality (HR = 1.4; 95% CI = 1.2-1.8; p<.001). Conclusion: We found that age at diagnosis was a significant predictor of the worse survival of GC patients diagnosed between 2015 and 2020 in Georgia.

Folic acid-mediated hollow Mn3O4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {Mn}_{3}\ ext {O}_{4}$$\\end{document} nanocomposites for in vivo MRI/FLI monitoring the metastasis of gastric cancer

BackgroundMetastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis.MethodsIn this paper, we constructed a new type of hollow Mn3O4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {Mn}_{3}\ ext {O}_{4}$$\\end{document} nanocomposites, Mn3O4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {Mn}_{3}\ ext {O}_{4}$$\\end{document}@HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of T1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext {T}_{1}}$$\\end{document}-weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging’s tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite.ResultsThis report demonstrates that Mn3O4\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ ext {Mn}_{3}\ ext {O}_{4}$$\\end{document}@HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future.ConclusionsIn vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI’s tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases.

Population attributable fractions of cancer mortality related to indoor air pollution, animal contact, and water source as environmental risk factors: Findings from the Golestan Cohort Study.

Environmental risk factors are significant contributors to cancer mortality, which are neglected. This study aimed to estimate the population attributable fraction of cancer mortality due to the environmental risk factors. Golestan cohort study is a population-base cohort on 50045 participants between 40-75 with about 18 years of follow up. We detected 2,196 cancer mortality and applied a multiple Cox model to compute the hazard ratio of environmental risk factor on all cancer and cancer-specific mortality. The population attributable fraction was calculated, accordingly. Biomass fuels for cooking, as an indoor air pollution, increased the risk of colorectal, esophageal, gastric cancer, and all-cancer mortality by 84%, 66%, 37%, and 17% respectively. Using gas for cooking, particularly in rural areas, could save 6% [Population Attributable Fraction: 6.36(95%CI: 1.82, 10.70)] of esophageal cancer, 3% [Population Attributable Fraction: 3.43 (0, 7.33)] of gastric cancer, and 6% [Population Attributable Fraction: 6.25 (1.76, 13.63)] of colorectal cancer mortality. Using a healthy tap water source could save 5% [Population Attributable Fraction:5.50(0, 10.93)] of esophageal cancer mortality, particularly in rural areas. There was no significant association between indoor air pollution for heating purposes and animal contact with cancer mortality. Considering the results of this study, eliminating solid fuel for most daily usage, among the population with specific cancer types, is required to successfully reduce cancer related mortality. Adopting appropriate strategies and interventions by policymakers such as educating the population, allocating resources for improving the healthy environment of the community, and cancer screening policies among susceptible populations could reduce cancer related mortalities.

Risk Scoring System to Predict Mortality in Gastric Cancer with Peritoneal Carcinomatosis.

Gastric cancer (GC) with peritoneal carcinomatosis (PC) has a particularly unfavorable prognosis. This limited survival raises doubts about which factors confer an extremely worse outcome and which patients could benefit from more aggressive treatments, in an attempt to improve survival and better control the disease. This study aimed to evaluate the survival outcomes of patients with PC due to GC and develop a prognostic score to predict 6-month mortality. We performed an analysis of clinical stage IV GC with PC. Scores were assigned to risk factors and calculated for each patient from nine variables. Among 326 IVB GC, 211 (64.7%) had PC and were included. After calculating the score, 136 (64.5%) GCs were classified as a low-risk group and 75 (35.5%) as a high-risk group. Median OS was 7.9 and 1.9 months for low- and high-risk patients (p < 0.001). In the high-risk group, 77.3% of the patients died in <6 mo (p < 0.001). Palliative surgery and chemotherapy were associated with better survival, and the prognostic groups maintained statistical significance even when the same type of treatment was performed. In conclusion, the scoring system developed with variables related to patient performance status and clinical data was able to distinguish GC with PC with a high risk of 6-month mortality. Accordingly, verifying and validating our findings in a large cohort of patients is necessary to confirm and guarantee the external validation of the results.

Advanced signet ring cell type gastroesophageal cancers in Latin American patients age 40 and below: A summary of one tertiary care center's experience and a review of the literature.

e16069 Background: Gastric Cancer mortality rates in Latin American countries of Central and South America (LA) are among the highest in the world. After observing multiple cases of advanced gastric adenocarcinoma (GA) with signet ring cell differentiation in young immigrants from LA, we sought to understand the prevalence and demographics of young-onset gastric cancer at our institution. Methods: We used the Inova Fairfax Hospital cancer registry to perform a retrospective cohort study by identifying all patients ≤ 40 from 2013-2022 with 1) GA, and 2) all cancers, and comparing the percentage of LA patients in each group. We noted a trend towards high rates of GC in young immigrants of LA six years ago, and now provide an updated analysis. We then reviewed phenotypic characteristics of each tumor, including signet ring cell differentiation, Her-2/Neu overexpression, and H. Pylori status and the time interval between diagnosis and death. Results: From 2013-2022, 21/37 patients (56.8%) ≤ 40 with GA were from LA (Table 1), with the majority from El Salvador. 95% (20/21) of LA patients had tumors with signet ring cell morphology, 88% (14/16) of non-LA patients had tumors with signet ring cell morphology. In comparison, patients that self-identified as “Hispanic/Spanish” made up 8.1% of subjects ≤ 40 with all cancers during the same time period. Conclusions: At our tertiary care center, Stage IV signet ring cell gastric cancer is highly prevalent in young patients from Latin America. Further exploration of epidemiological risk factors is warranted. [Table: see text]