Gastric cancer remains one of the deadliest cancers globally due to delayed detection and limited treatment options, underscoring the critical need for innovative prognostic methods. Disulfidptosis, a recently discovered programmed cell death triggered by disulphide stress, presents a fresh avenue for therapeutic exploration. This research examines disulfidptosis-related long noncoding RNAs (DRLs) in gastric cancer, with the goal of leveraging these lncRNAs as potential markers to enhance patient outcomes and treatment approaches. Comprehensive genomic and clinical data from stomach adenocarcinoma (STAD) were obtained from The Cancer Genome Atlas (TCGA). Employing least absolute shrinkage and selection operator (LASSO) regression analysis, a prognostic model was devised incorporating five key DRLs to forecast survival rates. The effectiveness of this model was validated using Kaplan-Meier survival plots, receiver operating characteristic (ROC) curves, and extensive functional enrichment studies. The importance of select lncRNAs and the expression variability of genes tied to disulfidptosis were validated via quantitative real-time PCR (qRT-PCR) and Western blot tests, establishing a solid foundation for their prognostic utility. Analyses of functional enrichment and tumour mutation burden highlighted the biological importance of these DRLs, connecting them to critical cancer pathways and immune responses. These discoveries broaden our comprehension of the molecular framework of gastric cancer and bolster the development of tailored treatment plans, highlighting the substantial role of DRLs in clinical prognosis and therapeutic intervention.

Gastric cancer (GC), one of the most prevalent malignancies worldwide, is distinguished by extensive genetic and phenotypic heterogeneity, posing persistent challenges to conventional diagnostic and therapeutic strategies. The significant global burden of GC highlights an urgent need to unravel its complex underlying mechanisms, discover novel diagnostic and prognostic biomarkers, and develop more effective therapeutic interventions. In this context, this review comprehensively examines the transformative roles of cutting-edge technologies, including radiomics, pathomics, genomics, transcriptomics, epigenomics, proteomics, and metabolomics, in advancing precision diagnosis and treatment for GC. Multiomics data analysis not only deepens our understanding of GC pathogenesis and molecular subtypes but also identifies promising biomarkers, facilitating the creation of tailored therapeutic approaches. Additionally, integrating multiomics approaches holds immense potential for elucidating drug resistance mechanisms, predicting patient outcomes, and uncovering novel therapeutic targets, thereby laying a robust foundation for precision medicine in the comprehensive management of GC.

DDX27, a member of the DEAD-box RNA helicase family, plays a crucial role in RNA metabolism, inflammation, and cancer progression. Elevated expression of DDX27 has been observed in multiple cancers, including oral squamous cell carcinoma (OSCC), breast cancer (BC), colorectal cancer (CRC), gastric cancer (GC), and hepatocellular carcinoma (HCC), where it is associated with poor prognosis, tumor growth, metastasis, and chemoresistance. DDX27 regulates the NF-κB signaling pathway, which is central to inflammation and tumor progression, and influences key cellular processes such as cell cycle regulation, apoptosis, migration, and stemness. Additionally, DDX27 promotes epithelial-mesenchymal transition (EMT), further contributing to metastasis. Its interactions with non-coding RNAs and various signaling pathways complicate treatment responses, making DDX27 a promising therapeutic target. This review explores the role of DDX27 as both a biomarker and therapeutic target, with potential strategies including small molecule inhibitors, RNA interference, and combination therapies with existing treatments such as NF-κB inhibitors or chemotherapy. Targeting DDX27 may help overcome resistance, reduce metastasis, and improve cancer treatment outcomes. Further research into its molecular mechanisms and interactions will be crucial for developing effective therapies, particularly for cancers with high metastatic potential.

Aims/Background Given the tremendous threat of stomach cancer (SC) to global public health, detailed information and dynamic updates on the SC health burden are needed to mitigate the repercussions. In this article, we present a systematic analysis of the global burden and trends of SC using data from the Global Burden of Disease (GBD) Study 2021, aiming to provide insights for forming effective global management and prevention strategies. Methods Stomach cancer incidence, prevalence, mortality, disability-adjusted life years (DALYs) and the corresponding age-standardized rates (ASRs) were estimated. Then, trends of the disease burden were analyzed using the estimated annual percentage changes (EAPC). Lastly, we made a unique attempt to use two powerful and versatile techniques, autoregressive integrated moving average (ARIMA) and exponential smoothing (ES) models, to provide more comprehensive and accurate forecasts for future trends in the disease burden. Results Despite the steady decreasing trend in age-standardized rates, the total numbers of incidence, prevalence, and deaths all increased from 1990 to 2021. Subgroup analysis demonstrated great disparities in different age and gender groups, sociodemographic index (SDI) quintiles, GBD regions and countries. Both the ARIMA and ES models demonstrated a persistent rise in SC cases and a concurrent decline in ASRs, with the trend being more pronounced in males. Conclusion Since SC is already a significant health issue globally, it is expected that the estimated disease burden will continue to rise in the future. Therefore, global coordinated efforts are needed to implement effective screening projects, consolidate preventive measures and formulate targeted treatments to alleviate the SC burden.

The application of robot-assisted technology in gastric cancer surgery is gradually gaining attention from surgeons. In this meta-analysis, our main objective was to assess whether robot-assisted techniques are more advantageous than laparoscopic-assisted technology in total gastrectomy.

We searched Pubmed, Embase, Web of Science, and Cochrane Library databases for clinical studies published before October 2023 comparing robotic-assisted total gastrectomy (RATG) and laparoscopic-assisted total gastrectomy (LATG) for gastric cancer. Non-clinical studies, data unavailability, or fewer than 50 included cases were excluded. The Newcastle-Ottawa Scale was used to assess the risk of bias by determining the quality of the observational studies. Statistical meta-analysis and drawing were performed using the Software Review Manager version 5.3 and Stata version 16.0. P < 0.05 was considered significant.

Nine studies that included 1,864 patients with gastric cancer were included, published between 2012 and 2023. The results of the analysis showed that RATG has advantages in the following aspects: intraoperative blood loss was 17.69 ml lower in the RATG group than in the LATG group (WMD: -17.69,95% CI:-20.90 ∼ -14.49; P < 0.05); In terms of the number of resected lymph nodes, the RATG group had 2.65 more than the LATG group (WMD: 2.65,95% CI:0.88 ∼ -4.42); P < 0.05); the time to start liquid and postoperative hospital stays were 0.62 and 0.90 days shorter in the RATG group than in the LATG group, respectively (WMD: -0.62,95%CI: -1.06 ∼ -0.19; P < 0.05), (WMD: -0.90,95%CI: -1.43 ∼ -0.37; P < 0.05)); the incidence of major complications and pancreas fistula in the RATG group was 0.59% and 0.17% lower than in the LATG group, respectively (OR: 0.59,95% CI: 0.38 ∼ 0.93; P < 0.05), (OR: 0.17,95% CI: 0.03 ∼ 0.94; P < 0.05). However, the analysis showed that the operative time in the RATG group was 30.96 min longer than in the LATG group (WMD: 30.96,95% CI: 21.24 ∼ 40.69; P < 0.05).

Based on the results of this meta-analysis, we concluded that robotic-assisted technology may be a worthwhile technique to apply in the surgical treatment of total gastrectomy. However, this meta-analysis has the limitations that the included studies were all non-randomized controlled trials and published in Asian countries, and more high-quality randomized controlled trials are needed for further validation in the future.

The study protocol for this meta-analysis is registered on the PROSPERO website under registration number CRD42024500512.

Exogenous microRNA-144 (miR-144) is considered as a potential biological drug for gastric cancer because of its biological activity to inhibit the epithelial-mesenchymal transition (EMT). However, the specific molecular mechanisms have not been fully revealed. In addition, their vulnerability to degradation by RNA enzymes in the blood limits their bioavailability. In this paper, a polyamidoamine (PAMAM)-wrapped miR-144 (PAMAM/miR-144) is prepared as a nanocarrier system to protect miR-144 from nuclease degradation. The PAMAM/miR-144 nanocarrier system achieves the optimal antitumor activity against gastric cancer migration and reduce mTOR protein expression by transferring miR-144 into human gastric cancer HGC-27 cells. At the same time, the PAMAM/miR-144 nanocarrier system significantly decreases the EMT via targeting mTOR signal pathway in HGC-27 cells and noticeably inhibited the growth of subcutaneous gastric cancer xenografts in nude mice. PAMAM/miR-144 nanocarrier system has effectively improved the bioavailability of miR-144, thus providing a promising combination modality for anticancer therapy.

Previous studies indicated that short-term outcomes for gastroenterological surgeries did not worsen during the COVID-19 pandemic. However, it remains unclear whether surgical volumes and medical resource use have recovered postpandemic. This study examines pre- and postpandemic trends in upper gastrointestinal surgeries, including esophagectomy and gastrectomy, and their short-term outcomes.

Data from the Japan's National Clinical Database (NCD) were analyzed for patients who underwent esophagectomy for esophageal cancer and gastrectomy for gastric cancer between January 2018 and December 2023. We evaluated changes in surgical volume, intensive care unit (ICU) use, morbidity, mortality rates, and the standardized morbidity and mortality ratio (SMR)-a comparison of observed versus expected outcomes using an NCD-established risk calculator. Key metrics included 30d mortality, surgical mortality, and four major morbidities like pneumonia and anastomotic leakage.

Esophagectomy volumes remained stable from 2018 to 2023, while gastrectomy volumes decreased notably over the past 6 y. The proportion of patients over 70 increased significantly in both surgery types. Morbidity and mortality rates showed no significant deterioration postpandemic, as indicated by SMR values.

This study analyzed changes in surgical volume and short-term outcomes for upper gastrointestinal cancer in the post-COVID-19 era using a Japanese nationwide database. It found that surgical treatments for gastrectomy and esophagectomy remained safe even after the pandemic.

With rapid social-economic development and widespread screening, the surge in incidence and overdiagnosis of thyroid cancer is more worrying among the young than the general population. This problem, however, still lacks adequate attention.

We retrieved the original data of current, past and future burden of thyroid cancer from the Global Cancer Observatory (GLOBOCAN) 2022. We calculated the age-specific mortality-to-incidence ratio (MIR) by dividing age-specific mortality rates by incidence rates to quantify potential overdiagnosis, and used Segi's world standard population to calculate the age-standardised incidence rate (ASIR) and age-standardised mortality rate (ASMR). We then assessed the correlation between the human development index (HDI) and ASIR/ASMR using the linear correlation coefficient (r). Lastly, we characterised the temporal trend with the estimated annual percentage change (EAPC) and project the early-onset thyroid cancer burdens to 2050.

Globally, there were an estimated 239 362 (ASIR = 4.00 per 100 000 population) cases and 2409 (ASMR = 0.04 per 100 000 population) deaths from thyroid cancer among individuals aged <40 years in 2022. Compared to its ranking as the 7th most common cancer in the overall population, thyroid cancer rose to become the 2nd most common cancer among individuals <40 years. Nearly 99% of thyroid cancer cases in individuals <40 years of age (MIR = 0.01) may be potentially overdiagnosed, whereas 34% of cases in those >80 years (MIR = 0.66) were overdiagnosed. The ASIR of early-onset thyroid cancer varied widely (from 0.13 to 13.17 per 100 000 population), while the ASMR remains relatively similar and low across different regions. The ASIR of early-onset thyroid cancer increased with HDI (r = 0.69), while the ASMR decreased (r = -0.22). The ASIR of early-onset thyroid cancer had the fastest upward trend (EAPC in males vs. females: 9.88 vs. 9.28%) compared to early-onset cancers at other sites, while ASMR showed a downward trend (EAPC in males vs. females: -0.38% vs. -1.33%). The Republic of Korea experienced the highest EAPC for early-onset thyroid cancer ASIR (males vs. females: 29.95% vs. 23.04%). If national rates from 2022 remain stable, projected cases of early-onset thyroid cancer would decrease in high (-13.3%) and very high (-10.9%) HDI countries, but increase in low (96.5%) and medium HDI countries (11.7%).

The trend of early-onset thyroid cancer at the global level is more alarming than that of thyroid cancer overall. The younger age at diagnosis of thyroid cancer, the higher risk of potential overdiagnosis. Without timely interventions, the thyroid cancer burden will inevitably become a serious global public health issue, especially for the young population.

PD-1 inhibitors combined with chemotherapy have become the standard first-line treatment for advanced gastric cancer (GC), but their efficacy in young GC patients is unknown. This study aimed to evaluate the efficacy of immunotherapy in young GC patients and explore new treatment strategies for this population.

Clinicopathological data of young unresectable GC patients were collected from multiple centres. We defined young as ≤45 years. Statistical analyses were conducted with SPSS IBM for Windows version 24.0.

In total, 225 young unresectable GC patients were registered. Their clinicodemographic characteristics included female predominance (60.9%), poor differentiation (86.7%), high family history of cancer (14.2%), low HER2 expression (12.2%), PD-L1 expression (43.0%) and mismatch repair (MMR) deficiency (1.0%), and a high proportion of peritoneal metastasis (49.3%). After screening, 134 patients were included for analysis: 63 received dual chemotherapy (mFOLFOX6, XELOX, SOX and two-drug containing paclitaxel), 32 PD-1 inhibitors plus dual chemotherapy (mFOLFOX6, XELOX, SOX and two-drug containing paclitaxel), and 39 triple regimens (two-drug chemotherapy combined with apatinib or trastuzumab, or triple chemotherapy based on platinum, fluorouracil and paclitaxel). The effectiveness analysis revealed no significant difference in the disease control rate (DCR) between the dual chemotherapy group and the PD-1 inhibitor plus dual chemotherapy group (P=0.787), but triple regimens led to the best DCR (71.4% vs. 68.8% vs. 94.9%, all P<0.05). Kaplan-Meier curves showed median progression-free survival (PFS) times of the three groups of 4.7, 4.7 and 9.2 months, respectively. The median overall survival (OS) was 13.9, 11.0 and 15.9 months, respectively. Multivariate analyses showed that triple regimens were an independent prognostic factor for PFS [hazard ratio (HR) 0.430, 95% confidence interval (CI) 0.263-0.700; P=0.001]. Detailed survival analysis demonstrated that patients receiving intraperitoneal infusion of paclitaxel followed by intravenous paclitaxel combined with S-1 and apatinib oral therapy had better PFS (P=0.014) and OS (P=0.013) than those receiving other regimens.

Young patients with GC have unique clinical characteristics and are not sensitive to immunotherapy. Triple regimens, especially intraperitoneal infusion of paclitaxel followed by intravenous paclitaxel combined with S-1 and apatinib oral therapy, deserve to be studied as first-line therapies.

Gastric cancer (GC) prognosis is significantly influenced by intratumoral microbiomes, which modulate host-immune interactions. This study analyzed data from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to identify immune genes associated with GC prognosis and conducted prognostic immune subtypes. GC patients were classified into two distinct prognostic immune phenotypes C1 and C2 based on the non-negative matrix factorization consensus clusters. Phenotype C2 exhibited a better prognosis and distinct immune characteristics, including enhanced presence of Th2 and Th17 cells and improved response to chemotherapy. In contrast, phenotype C1 showed higher expression levels of PDCD1LG2 and TLR9, which were critical immune factors involved in immune regulation. Both phenotypes were linked to immune genes influencing intratumoral microbiomes and GC immunotherapy responses. A prediction risk model was constructed using the LASSO regression analysis and showed great prognostic value for GC patients. The key genes were correlated with immune cells and suppressed the function of the host immune system. The intratumoral microbiomes were strongly associated with the hosts' immune infiltration and significantly interacted with host immune genes to influence GC outcomes. Candidatus Nitrosotenuis plays a significant role in predicting the prognosis of GC patients. This research underscores the pivotal role of intratumoral microbiomes in GC prognosis and supports the development of future personalized therapeutic approaches.IMPORTANCEIncreasing evidence confirms the presence of intratumoral microbiomes. However, the role of the intratumoral microbiomes in the progression of gastric cancer and their relationship with the immune microenvironment remain unclear. Our study classified gastric cancer patients into two immune prognostic subtypes, C1 and C2, using non-negative matrix factorization consensus clusters. The C2 subtype exhibited a better prognosis and more pronounced immune characteristics. Microbiome analyses revealed associations between both subtypes and immune genes that affect intratumoral microbiomes and their responses to immunotherapy. The intratumoral microbiomes were closely linked with host immune infiltration and significantly interacted with immune genes, which influence the prognosis of gastric cancer. Notably, Candidatus Nitrosotenuis showed a significant prognostic value in gastric cancer patients. Our findings highlight the critical role of the intratumoral microbiomes in affecting gastric cancer prognosis and its interaction with the immune microenvironment, supporting future personalized therapeutic approaches.

Despite advances in systemic therapy, metastatic gastric cancer is associated with a poor prognosis. As peritoneal disease is common, several studies looked at the potential benefits of hyperthermic intraperitoneal chemotherapy (HIPEC) in this context, with encouraging results. However, no Canadian data currently exists on the subject.

This study aims to report characteristics and outcomes of Canadian patients who underwent cytoreductive surgery and HIPEC (CRS-HIPEC) for gastric cancer associated with peritoneal disease or positive peritoneal cytology. This multicenter retrospective study included patients 18 years or older with gastric cancer associated with isolated peritoneal involvement who underwent CRS-HIPEC in five tertiary centers from 2016 to 2022.

CRS-HIPEC was performed on 20 patients aged 34-69 years old, most of whom presented with poorly differentiated (90 %) adenocarcinoma, with synchronous peritoneal disease (95 %). Median PCI was 3 (0-13). The associated 90-day morbidity rate, defined as Clavien-Dindo grade III and above complications, was 10 %. At a mean follow-up of 23.3 months (range 4-48), 25 % of patients remained disease-free, with an estimated median overall survival of 24.2 months.

CRS-HIPEC for gastric cancer can achieve longer term survival in highly selected patients with low-burden peritoneal disease or positive cytology. Ongoing randomized trials will further clarify patients' selection criteria and benefits of this approach.

Despite extensive research on gastric cancer (GC), efforts to consolidate the numerous associations between possible factors and GC risk remain lacking. This systematic review aimed to provide an overview of potential GC-associated pairs.

We systematically searched PubMed, Embase, and Cochrane databases, from their inception to April 23, 2022, for eligible systematic reviews and meta-analyses to investigate the association between any possible factors and GC risk. After the inclusion of 75 systematic reviews and meta-analyses, 117 association pairs were examined. We reanalyzed the included meta-analyses and produced effect estimates using uniform analytical models. The certainty of the evidence for each association pair was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria.

Iatrogenic factors, including antibacterial drugs, were associated with an increased risk of GC. Epstein-Barr virus and Helicobacter pylori infections were also associated with an increased risk of GC, while human T-lymphotropic virus type 1 (HTLV-1) infections were associated with a reduced risk. Dietary habit was a major factor influencing moderate to high GRADE associations. Positive associations were observed for heavy alcohol consumption (relative risk [RR], 1.13; 95% confidence interval [CI], 1.06-1.12), refined grain consumption (RR, 1.36; 95% CI, 1.21-1.53), and habitual salt intake (RR, 1.41; 95% CI, 1.04-1.91).

The associations between GC risk and dietary and nutritional factors were considerably heterogeneous, whereas other factors, such as lifestyle and iatrogenic and environmental exposures, were consistent across regions. Therefore, dietary interventions for GC prevention should be tailored specific to regions.

PROSPERO Identifier: CRD42020209817.

Elderly gastric cancer patients undergoing radical gastrectomy are prone to experience unexpected weight loss. Preoperative weight risk prediction may be a promising way to prevent weight loss and improve prognosis. The objectives of this study were to explore the BMI trajectory of elderly gastric cancer patients one year after surgery, evaluate theirs the association with outcomes, and explore their related predictors, so as to provide evidence for weight management and prognosis improvement.

412 gastric cancer patients were included and recorded BMI at 6 time points. The trajectories of BMI were analyzed by growth mixture modeling, and the associations of BMI trajectories with outcomes as well as their predictors were investigated by regression models.

We identified 3 classes of BMI trajectories: the "slow-decreasing BMI", "rapid-decreasing BMI" and "maintaining BMI". Compared with class1, patients in class 2 were more likely to have a higher frequency of readmission within 1-year(β = 0.59, 95%CI: 0.29, 0.89, P < 0.001) and a higher rate of mortality within 1-year(β = 24.74, 95%CI: 9.60, 63.74, P < 0.001) ; patients in class 3 were more likely to have a higher quality of life (β=-10.46, 95%CI: -17.70, -3.22, P = 0.005) and fewer readmission times within one year (β=-0.43, 95%CI: -0.77, -0.09, P = 0.015). Predictors of decreasing BMI trajectories were TNM stage, comorbidity, anxiety, family cohesion and social support(P < 0.05).

Our findings can provide a basis for screening high-risk elderly gastric cancer patients with poor prognosis, implementing risk stratification, formulating accurate weight management programs and improving prognosis.

The results of our study can provide gastric cancer survivors with preoperative risk screening based on predictive factors so that nutritional support and weight management can be implemented in a timely manner to improve prognosis.

Early-onset gastric cancer (EOGC) is a lethal malignancy. It differs from late-onset gastric cancer (LOGC) in clinical and molecular characteristics. The current strategies for EOGC detection have certain limitations in diagnostic performance due to the rising trend in EOGC.

We developed a liquid biopsy signature for EOGC detection.

We use a systematic discovery approach by analysing genome-wide transcriptomic profiling data from EOGC (n=43), LOGC (n=31) and age-matched non-disease controls (n=37) tissue samples. An extracellular vesicle-derived long non-coding RNA (EV-lncRNA) signature was identified in blood samples from a training cohort (n=299), and subsequently confirmed by qPCR in two external validation cohorts (n=462 and n=438), a preoperative/postoperative cohort (n=66) and a gastrointestinal tumour cohort (n=225).

A three EV-lncRNA (NALT1, PTENP1 and HOTTIP) liquid biopsy signature was developed for EOGC detection with an area under the receiver operating characteristic curve (AUROC) of 0.924 (95% CI 0.889 to 0.953). This EV-lncRNA signature provided robust diagnostic performance in two external validation cohorts (Xi'an cohort: AUROC, 0.911; Beijing cohort: AUROC, 0.9323). Furthermore, the EV-lncRNA signature reliably identified resectable stage EOGC patients (stage I/II) and demonstrated better diagnostic performance than traditional GC-related biomarkers in distinguishing early-stage EOGC (stage I) from precancerous lesions. The low levels of this biomarker in postsurgery and other gastrointestinal tumour plasma samples indicated its GC specificity.

The newly developed EV-lncRNA signature effectively identified EOGC patients at a resectable stage with enhanced precision, thereby improving the prognosis of patients who would have otherwise missed the curative treatment window.

This study examined global trends in influenza-associated lower respiratory infections (LRIs) deaths from 1990 to 2019 using data from the GBD 2019. The annual percentage change (APC) and average annual percentage change (AAPC) were used to analyze age-standardized death rates (ASDR). Globally, the ASDR of influenza-associated LRIs was 3.29/100,000 in 2019, which was higher in the African region (6.57/100,000) and among adults aged 70 years and older (29.88/100,000). The ASDR of influenza-associated LRIs decreased significantly from 1990 to 2019 (AAPC = -1.88%, P < 0.05). However, it was significantly increased among adults aged 70 years and older during 2017-2019 (APC = 2.31%, P < 0.05), especially in Western Pacific Region and South-East Asia Regions. The ratio of death rates between adults aged 70 years and older and children aged under 5 years increased globally from 1.63 in 1990 to 5.34 in 2019, and the Western Pacific Region experienced the most substantial increase, with the ratio soaring from 1.83 in 1990 to 12.98 in 2019. Despite a decline in the global ASDR of influenza-associated LRIs, it continues to impose a significant burden, particularly in the African, Western Pacific regions and among the elderly population.

Immunotherapy has surfaced as a promising therapeutic modality for gastric cancer (GC). A comprehensive review of advancements, current status, and research trends in GC immunotherapy is essential to inform future investigative efforts.

To delineate the trends, advancements, and focal points in immunotherapy for GC.

We performed a bibliometric analysis of 2906 articles in English concerning GC immunotherapy published from 2000 to December 20, 2023, indexed in the Web of Science Core Collection. Data analysis and visualization were facilitated by CiteSpace (6.1.6R), VOSviewer v.1.6.17, and GraphPad Prism v8.0.2.

There has been an increase in the annual publication rate of GC immunotherapy research. China leads in publication volume, while the United States demonstrates the highest citation impact. Fudan University is notable for its citation frequency and publication output. Co-citation analysis and keyword frequency revealed and highlighted a focus on GC prognosis, the tumor microenvironment (TME), and integrative immunotherapy with targeted therapy. Emerging research areas include gastroesophageal junction cancer, adoptive immunotherapy, and the role of Treg cell in immunotherapy.

GC immunotherapy research is an expanding field attracting considerable scientific interest. With the clinical adoption of immunotherapy in GC, the primary goals are to enhance treatment efficacy and patient outcomes. Unlike hematological malignancies, GC's solid TME presents distinct immunological challenges that may attenuate the cytotoxic effects of immune cells on cancer cells. For instance, although CAR-T therapy is effective in hematological malignancies, it has underperformed in GC settings. Current research is centered on overcoming immunosuppression within the TME, with a focus on combinations of targeted therapy, adoptive immunotherapy, Treg cell dynamics, and precise prognosis prediction in immunotherapy. Additionally, immunotherapy's role in treating gastroesophageal junction cancer has become a novel research focus.

Histone lactylation, a novel epigenetic modification, is regulated by the lactate produced by glycolysis. Glycolysis is activated in various cancers, including gastric cancer (GC). However, the molecular mechanism and clinical impact of histone lactylation in GC remain poorly understood. Here, we demonstrate that histone H3K18 lactylation (H3K18la) is elevated in GC, correlating with a worse prognosis. SIRT1 overexpression decreases H3K18la levels, whereas SIRT1 knockdown increases H3K18la levels in GC cells. RNA-seq analysis demonstrates that lncRNA H19 is markedly downregulated in GC cells with SIRT1 overexpression and those grown under glucose free condition, which confirmed decreased H3K18la levels at its promoter region. H19 knockdown decreased the expression levels of LDHA and H3K18la, and LDHA knockdown impaired H19 and H3K18la expression, suggesting an H19/glycolysis/H3K18la-positive feedback loop. Combined treatment with low doses of the SIRT1-specific activator SRT2104 and the LDHA inhibitor oxamate exerted significant antitumor effects on GC cells, with limited adverse effects on normal gastric cells. The SIRT1-weak/H3K18la-strong signature was found to be an independent prognostic factor in patients with GC. Therefore, SIRT1 acts as a histone delactylase for H3K18, and loss of SIRT1 triggers a positive feedback loop involving H19/glycolysis/H3K18la. Targeting this pathway serves as a novel therapeutic strategy for GC treatment.

SR-like CTD-associated factor 8 (SCAF8) can regulate transcriptional termination, but the function of circSCAF8 remains unclear. In our study, we observed a significant increase in circSCAF8 expression in gastric cancer, particularly in tissues with lymph node metastasis. The Kaplan-Meier curve revealed that high circSCAF8 expression was associated with a low overall survival time in gastric cancer patients. Moreover, circSCAF8 shRNA effectively decreased gastric cancer proliferation, invasion, and migration in vitro. Additionally, using bioluminescence imaging (BLI) technology in vivo, we found that circSCAF8 shRNA viruses inhibited the growth of xenograft tumors and gastric cancer lung metastasis. RNA immunoprecipitation (RIP) and circRNA pulldown assays confirmed the direct binding of circSCAF8 to miR-1293, but circSCAF8 could not regulate the expression of miR-1293 in gastric cancer. Interestingly, circSCAF8 regulated the downstream gene tissue inhibitor of metalloproteinases 1 (TIMP1) of miR-1293, and this observation was further verified in gastric cancer tissues. Moreover, we confirmed that miR-1293 directly suppressed TIMP1 expression. Subsequent rescue experiments revealed that TIMP1 overexpression reversed the impact of circSCAF8 shRNA viruses on gastric cancer. In conclusion, circSCAF8 expression was elevated in gastric cancer, and circSCAF8 shRNA viruses inhibited gastric cancer growth and metastasis by upregulating TIMP1 expression via miR-1293.

Stomach cancer is one of the leading causes of cancer death, and its epidemiologic characteristics are regionally heterogeneous worldwide. The BRICS nations (Brazil, Russian Federation, India, China, and South Africa) have markedly increasing influences on the international stage. We aim to investigate time trends in stomach cancer mortality among the BRICS countries from 1982 to 2021.

Data for this study were obtained from the Global Burden of Disease (GBD) 2021 public dataset to investigate the deaths, all-age mortality rate, and age-standardized mortality rate (ASMR) of stomach cancer. The age-period-cohort (APC) model was employed to estimate net drift, local drift, age-specific curves, and period (cohort) relative risks, and the Bayesian generalized linear model was employed to evaluate the relationship between food intake and mortality rate.

In 2021, there were approximately 572,000 stomach cancer deaths across the BRICS, accounting for 59.9% of global death. Russian Federation exhibited the most significant reduction in ASMR of stomach cancer among the BRICS. In contrast, China continued to report the highest number of stomach cancer deaths. The risk of mortality associated with stomach cancer exhibited a marked increase with advancing age, both within these countries and at the global level. PUFA, sodium, calcium and trans fat may have an impact on the mortality rate of stomach cancer. Favorable trends in period and birth cohort effects were observed in these five nations over the past decades.

BRICS countries have made varying progress in reducing stomach cancer mortality. Given the diverse environments, it is recommended to progressively develop customized stomach cancer prevention strategies, utilizing available resources. Healthcare services should be extended to all age groups, with a particular emphasis on vulnerable populations.

In recent years, the global prevalence of gastric cancer (GC) has witnessed a progressive decrease, accompanied by a step-growth in the incidence of gastric signet ring cell carcinoma (GSRCC). As precision medicine concepts progress, GSRCC, a distinct sub-type of GC, has drawn considerable attention from researchers. However, there still persist some controversies regarding the associated research findings.

To summarize the current obstacles and potential future directions for research on GSRCC.

To begin with, all literature related to GSRCC published from January 1, 2004 to December 31, 2023 was subjected to bibliometric analysis in this article. Additionally, this paper analyzed the research data using CiteSpace, GraphPad Prism v8.0.2, and VOSviewer, which was obtained from the Web of Science Core Collection database. The analysis results were visually represented.

This study provided a comprehensive overview of the statistical characteristics of the 995 English articles related to GSRCC, including cited references, authors, journals, countries, institutions, and keywords. The popular keywords and clusters contain "prognosis", "survival", "expression", "histology", and "chemotherapy".

The prognosis, precise definition and classification, as well as chemoresistance of GSRCC, continue to be crucial areas of ongoing research, whose directions are closely tied to advancements in molecular biology research on GSRCC.

Gastric cancer represents a major public health burden globally, with a disproportionately high incidence and mortality observed in Asian countries. To analyze the epidemiology of gastric cancer across Asia using data from the GLOBOCAN 2020 database and explore the potential correlations with socioeconomic indicators. The study reported numbers of cases, 5-year prevalence, crude and age-standardized rates of incidence (ASIR) and mortality (ASMR), mortality-to-incidence ratio (MIR), and cumulative risk percentages. Asia had the highest ASIR and ASMR of gastric cancer in the world in 2020, with 14.30 and 10.00 per 100,000 population, respectively. The ASIRs were 20.40 and 8.70 in Asian males and females, respectively. The ASMRs were also 14.20 and 6.20 in males and females, respectively. The incidence and mortality rates increased with age and peaked in the > 70-year age group. There was a moderate inverse correlation between MIR and human development index (HDI). The incident cases of gastric cancer and its mortality numbers in Asia are estimated to increase by 72.20% and 75.90% by 2040, respectively. Gastric cancer burden varies across Asia, with high incidence and mortality rates in Eastern Asia. Lower MIRs in socioeconomically developed nations suggest the impact of early detection and treatment access to improve patients' outcomes.

Gastric cancer remains one of the most common cancers and the leading cause of death in China. This study aims to describe the incidence, mortality, survival rates, and their changing trends of gastric cancer in Xiamen, China from 2011 to 2020.

Population-based cancer registry data were used to calculate the incidence, mortality, and survival rates of gastric cancer. The study population consisted of gastric cancer patients diagnosed from January 1, 2011, to December 31, 2020, and followed up until September 30, 2023. The relative survival of gastric cancer was calculated using period methods. The change in trends was analyzed using Joinpoint regression.

From 2011-2020, a total of 4716 new cases of gastric cancer and 3520 related deaths were reported. The crude incidence rate and age-standardized incidence rate (ASIR) were 21.82/100,000 and 16.74/100,000. The crude mortality rate and age-standardized mortality rate (ASMR) were 16.29/100,000 and 12.30/100,000. The ASIR and ASMR in males (ASIR: 24.71/100,000, ASMR: 18.75/100,000) were both more than those in females (ASIR: 9.6/100,000, ASMR: 6.55/100,000). The observed 5-year survival rate was 25.83 %, with an age standardized survival of 27.60 %. The incidence and mortality of gastric cancer showed a decreasing trend, and the 5-year ARS between 2016 and 2020 (30.03 %, 95 %CI: 28.07-32.12 %) was higher than between 2011 and 2015 ( 24.79 %, 95 %CI: 22.53-27.27 %). Furthermore, the survival rate decreased with increasing age.

From 2011-2020, the incidence and mortality of gastric cancer in Xiamen City have shown a decreasing trend, and the survival rate has significantly improved. Despite improved survival, the 5-year ARS remains low.

to investigate trends in gastric cancer (GC) incidence in Spain from 1990 to 2019, analyzing variations by sex and age.

GC incidence data from the Global Burden of Disease database and population data from the Spanish National Institute of Statistics were used to calculate age-specific and age-standardized incidence rates (ASIR) with the European population as the reference. Temporal trends by sex and age groups were analyzed using joinpoint regression.

while the total number of cases increased slightly, ASIR showed a consistent annual decrease of 1.8 % for both men and women. Both sexes experienced this increase in total cases (women: 4,023 to 4,359; men: 6,243 to 6,591). Men consistently had a higher GC burden compared to women (approximately 2.2:1 ratio). Younger adults (< 35 years) of both sexes showed significant decreases in ASIR. However, the joinpoint analysis revealed a recent increase in young men (25-34 years) during the period 2014-2019. Adults aged 35-64 showed a decrease in ASIR for both sexes, with a slightly steeper decline in men. Adults over 65 had a similar decrease in ASIR for both sexes, but the joinpoint analysis suggests different patterns within this age group.

our study revealed a decline in overall age-adjusted GC incidence in Spain. However, the recent rise observed in young men warrants further investigation to understand potential risk factors in this specific population group.

Signal regulatory protein alpha (SIRPα) inhibits phagocytosis by macrophages by interacting with CD47. Despite its known role in various cancers, the clinical significance of SIRPα in gastric cancer (GC) remains unclear. This study aimed to elucidate the clinical implications of SIRPα in GC, exploring its relevance to immunotherapy efficacy and the tumor microenvironment.

Two cohorts were studied: a gastrectomy cohort (137 patients) and an immune checkpoint inhibitor (ICI)-treated cohort (19 patients with unresectable advanced GC who received nivolumab). Immunohistochemistry was used to assess SIRPα, CD80, CD163, CD8, and PD-L1 expressions. Kaplan-Meier curves and Cox models were used to analyze the clinical outcomes. In vitro experiments used peripheral blood mononuclear cells and THP-1 macrophage cell lines to examine SIRPα responses to interferon-γ (IFN-γ).

In the gastrectomy cohort, high SIRPα expression correlated with advanced tumor invasion, distant metastasis, and poor recurrence-free and overall survival. SIRPα expression was also significantly associated with macrophage and CD8 + T cells infiltration and PD-L1 expression. In the ICI-treated cohort, high SIRPα expression was associated with better overall survival after nivolumab induced. Moreover, in vitro IFN-γ stimulation upregulated SIRPα expression on monocytes in peripheral blood mononuclear cells and THP-1 cells, suggesting high SIRPα expression may reflect an active immune microenvironment.

SIRPα expression is not only a poor prognostic factor for GC, possibly through inhibition of the CD47-SIRP⍺ pathway, but may also be involved in the efficacy of ICI therapy in GC.

Cancers of the digestive system are major contributors to global cancer-associated morbidity and mortality, accounting for 35% of annual cases of cancer deaths. The etiologies, molecular features, and therapeutic management of these cancer entities are highly heterogeneous and complex. Over the last decade, genomic and functional studies have provided unprecedented insights into the biology of digestive cancers, identifying genetic drivers of tumor progression and key interaction points of tumor cells with the immune system. This knowledge is continuously translated into novel treatment concepts and targets, which are dynamically reshaping the therapeutic landscape of these tumors. In this review, we provide a concise overview of the etiology and molecular pathology of the six most common cancers of the digestive system, including esophageal, gastric, biliary tract, pancreatic, hepatocellular, and colorectal cancers. We comprehensively describe the current stage-dependent pharmacological management of these malignancies, including chemo-, targeted, and immunotherapy. For each cancer entity, we provide an overview of recent therapeutic advancements and research progress. Finally, we describe how novel insights into tumor heterogeneity and immune evasion deepen our understanding of therapy resistance and provide an outlook on innovative therapeutic strategies that will shape the future management of digestive cancers, including CAR-T cell therapy, novel antibody-drug conjugates and targeted therapies.

Advanced gastric cancer (GC) exhibits a high recurrence rate and a dismal prognosis. Myocyte enhancer factor 2c (MEF2C) was found to contribute to the development of various types of cancer. Therefore, our aim is to develop a prognostic model that predicts the prognosis of GC patients and initially explore the role of MEF2C in immunotherapy for GC.

Transcriptome sequence data of GC was obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO) and PRJEB25780 cohort for subsequent immune infiltration analysis, immune microenvironment analysis, consensus clustering analysis and feature selection for definition and classification of gene M and N. Principal component analysis (PCA) modeling was performed based on gene M and N for the calculation of immune checkpoint inhibitor (ICI) Score. Then, a Nomogram was constructed and evaluated for predicting the prognosis of GC patients, based on univariate and multivariate Cox regression. Functional enrichment analysis was performed to initially investigate the potential biological mechanisms. Through Genomics of Drug Sensitivity in Cancer (GDSC) dataset, the estimated IC50 values of several chemotherapeutic drugs were calculated. Tumor-related transcription factors (TFs) were retrieved from the Cistrome Cancer database and utilized our model to screen these TFs, and weighted correlation network analysis (WGCNA) was performed to identify transcription factors strongly associated with immunotherapy in GC. Finally, 10 patients with advanced GC were enrolled from Sun Yat-sen University Cancer Center, including paired tumor tissues, paracancerous tissues and peritoneal metastases, for preparing sequencing library, in order to perform external validation.

Lower ICI Score was correlated with improved prognosis in both the training and validation cohorts. First, lower mutant-allele tumor heterogeneity (MATH) was associated with lower ICI Score, and those GC patients with lower MATH and lower ICI Score had the best prognosis. Second, regardless of the T or N staging, the low ICI Score group had significantly higher overall survival (OS) compared to the high ICI Score group. For its mechanisms, consistently, for Camptothecin, Doxorubicin, Mitomycin, Docetaxel, Cisplatin, Vinblastine, Sorafenib and Paclitaxel, all of the IC50 values were significantly lower in the low ICI Score group compared to the high ICI Score group. As a result, based on univariate and multivariate Cox regression, ICI Score was considered to be an independent prognostic factor for GC. And our Nomogram showed good agreement between predicted and actual probabilities. Based on CIBERSORT deconvolution analysis, there was difference of immune cell composition found between high and low ICI Score groups, probably affecting the efficacy of immunotherapy. Then, MEF2C, a tumor-related transcription factor, was screened out by WGCNA analysis. Higher MEF2C expression is significantly correlated with a worse OS. Moreover, its higher expression is also negatively correlated with tumor mutation burden (TMB) and microsatellite instability (MSI), but positively correlated with several immunosuppressive molecules, indicating MEF2C may exert its influence on tumor development by upregulating immunosuppressive molecules. Finally, based on transcriptome sequencing data on 10 paired tumor tissues from Sun Yat-sen University Cancer Center, MEF2C expression was significantly lower in paracancerous tissues compared to tumor tissues and peritoneal metastases, and it was also lower in tumor tissues compared to peritoneal metastases, indicating a potential positive association between MEF2C expression and tumor invasiveness.

Our prognostic model can effectively predict outcomes and facilitate stratification GC patients, offering valuable insights for clinical decision-making. The identified transcription factor MEF2C can serve as a biomarker for assessing the efficacy of immunotherapy for GC.

Previous studies have demonstrated that PNI can predict the prognosis of gastric cancer (GC) patients. However, few studies have focused on the auxiliary role of miRNA in predicting the prognosis of GC.

This research seeks to clarify the role of the combined use of miR-132-3p and PNI in predicting the prognosis of GC patients.

The qRT-PCR was used to assess the expression of miR-132-3p in tumor and adjacent normal tissues with GC patients. The predictive value of miR-132-3p and PNI for postoperative prognosis, and the relationships between miR-132-3p, PNI, and preoperative clinical characteristics, were assessed using ROC, χ², Kaplan-Meier survival analysis, and Cox regression analysis.

miR-132-3p was found to be downregulated in GC tumor tissues and significantly positively correlated with PNI. Both miR-132-3p and PNI were significantly associated with TNM stage and lymph node metastasis. Postoperative GC patients with low miR-132-3p expression and low PNI had lower survival rates, and both were independent risk factors for poor prognosis. The combination of miR-132-3p and PNI demonstrated better sensitivity and specificity in predicting postoperative prognosis than either indicator alone.

The combination of miR-132-3p and PNI can effectively improve the predictive value of postoperative prognosis in GC patients.

Gastric cancer (GC) remains a significant global health challenge, characterized by high incidence and mortality rates, particularly in East Asia. A comprehensive understanding of the disease burden of gastric cancer is crucial for developing effective prevention and treatment strategies. However, comprehensive global assessments of the disease burden of gastric cancer remain limited. This study, based on the Global Burden of Disease (GBD) framework, systematically analyzes global trends in gastric cancer from 1990 to 2021 and projects future trends through 2035, aiming to provide scientific evidence for policymaking.

The data were derived from the Global Burden of Disease (GBD) Study 2021, covering gastric cancer (GC) incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs), and age-standardized DALY rates (ASRs) across 204 countries and regions from 1990 to 2021. The Bayesian age-period-cohort model was employed to project trends up to 2035.

In comparison with 1990, both the incidence and mortality of GC rose in 2021, with over 1.23 million new cases recorded globally, resulting in 954,373.60 deaths and 22,786,633.10 DALYs. Between 1990 and 2021, the ASIRs, ASDRs, and ASRs decreased by 42% (ranging from 49 to 35%), 49% (ranging from 55 to 43%), and 53% (ranging from 58 to 47%), respectively. The peak ASIRs and ASDRs in 2021 were seen in the high-middle SDI quintile. Males exhibited higher rates of ASDRs, ASIRs, and ASRs compared to females. In 2021, East Asia and high-income North America bore the largest burden of smoking-related GC, while Central Europe experienced the highest burden from high-sodium diets. Forecasts toward 2035 indicate a continued decline in both ASIRs and ASDRs.

Despite notable reductions in both incidence and mortality, GC remains a substantial global burden, affecting various regions and countries. Deaths and DALYs related to high-sodium diets and smoking have shown an overall decline. However, substantial regional and age-related disparities persist. Targeted interventions, such as smoking control and promoting the intake of fresh fruits and vegetables, are essential in diminishing GC risk.

Laparoscopic distal gastrectomy is now widely used in East Asia and worldwide with different preferences and outcomes. This study aimed to compare the short- and long-term outcomes and preferences between two high-volume gastric cancer centers in Korea and China.

Patients who underwent laparoscopic-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer from Seoul National University Hospital (SNUH) and the First Affiliated Hospital of Nanjing Medical University (NMUH) from 2017 to 2020 were enrolled in this study.

A total of 1166 SNUH cases and 847 NMUH cases enrolled in this study. The overall complication rate of SNUH (14.49%) did not differ from that of NMUH after LADG or TLDG (12.28%). The anastomosis-related complications rate (2.74%) did not show a significant difference with that of NMUH (2.01%) either. The median postoperative hospital stay for SNUH (7,(7,10)) was shorter than that for NMUH (8,(7,9)). The 5-year overall survival (OS) rate of SNUH was not significantly different from that of NMUH.

There was no significant difference in the overall complication rate, anastomosis-related complication rate, resected lymph nodes, and 5- year overall survival rate between SNUH and NMUH except for the postoperative stay. Both the LADG and TLDG achieved satisfactory short- and long-term outcomes when performed by surgeons with adequate experience.

Gastric cancer is a common malignancy with a high incidence in East Asia. Gastric resection ranges from endoscopic resection to open total gastrectomy. However, nationwide data are lacking.

This observational study analyzed data from the publicly accessible National Database of Health Insurance Claims and Specific Health Checkups, which includes most national health insurance claims data in Japan. Trends in the types of resection performed for malignant gastric tumors between 2014 and 2021, patients' age and sex distributions, and regional disparities were investigated.

The annual number of resections was highest in 2015 (109,000) and lowest in 2020 (90,000) after the COVID-19 pandemic. The proportion of endoscopic resections increased from 47% in 2014 to 57% in 2021 while that of total gastrectomies decreased from 17 to 10%. In 2021, 70% of patients who underwent resection were men. That year, 83.8% of all patients who underwent any type of gastric resection and 87.1% of those who underwent endoscopic submucosal dissection were aged ≥ 65 years. The annual incidence of gastric resection per million population was highest in Tottori (n = 1236) and lowest in Okinawa (n = 251). The proportion of endoscopic resections was highest in Miyagi (66%) and lowest in Aichi (45%) and that of open surgery was highest in Aomori (36%) and lowest in Wakayama (5%).

Gastric malignancy is increasingly treated by endoscopic submucosal dissection rather than open total gastrectomy. However, regional disparities remain in resection type. Standardization of treatment and a more even distribution of specialists are needed.

Gastric precancerous lesions (GPL) typically originates from chronic gastritis (CG), and the changes in glycolysis mediated by the HIF-1α pathway during the progression from CG to GPL are unclear. Modified Zuojin pill (SQQT) is a traditional Chinese herbal formula used for treating GPL. However, the underlying mechanism has not been fully elucidated.

To investigate the changes in glycolysis mediated by the HIF-1α pathway during the progression from CG to GPL and whether SQQT can alleviate GPL by attenuating glycolysis through the HIF-1α pathway.

A rat model of GPL was established, and the changes of glycolysis mediated by the HIF-1α pathway during the progression from CG to GPL were detected in 12th, 18th, 24th, and 30th weeks. The therapeutic efficacy of SQQT was evaluated through pathological changes. In vitro, the GPL cell model (MC cell) originated from GES-1 cells intervened by MNNG. The effects of SQQT on glycolysis and the HIF-1α pathway were detected in vivo and in vitro. In vitro, HIF-1α overexpression was used to confirmed that SQQT attenuated glycolysis by targeting the HIF-1α pathway.

Our study revealed that glycolysis mediated by the HIF-1α pathway exhibited dynamic changes in the progression from CG to GPL, characterized by sequential activation, deactivation, and reactivation. SQQT ameliorated gastric mucosal pathology and inflammation in GPL rats. Mechanistic studies revealed that SQQT alleviated glycolysis by targeting the HIF-1α pathway, and improved abnormal cellular proliferation and apoptosis. Importantly, HIF-1α overexpression blocked the effect of SQQT on glycolysis.

In the progression from CG to GPL, the HIF-1α pathway-mediated glycolysis was characterized by sequential activation, deactivation, and reactivation. SQQT attenuated glycolysis by targeting the HIF-1α pathway and improved abnormal cellular proliferation and apoptosis in the gastric mucosa, thereby exerting therapeutic effects on GPL.

Cancer is a major cause of mortality. Timely information about cancer mortality trends is essential for prioritizing health programs.

This study aims to use a Joint point regression model to predict the mortality rates of the top 10 common cancers in Babol City.

This cross-sectional study considered all registered cancer-related deaths from 2013 to 2021 in the Babol University of Medical Sciences' death registration and classification system. Crude and age-standardized rates and cancer trends were calculated and predicted for the next 5 years, overall and by type of cancer and gender.

Over these 9years, 2417 deaths from the 10 common cancers were recorded. We observed an increase in mortality rates with a slope of 12.05% from 2013 to 2016, and a gentler slope of 3.2% from 2016 to 2021. Cancer mortality rates are predicted to increase by 6.43% in the next 5 years without intervention. Detailed analysis indicates that breast cancer will have the highest mortality rate during 2022-2026, rising by 13.6% annually. Predictions based on gender indicate that, breast cancer mortality will increase by 13.6% annually for women. Also, stomach cancer mortality rates will increase by 0.15% in men annually.

Cancer mortality in Babol remains a significant public health issue with an increasing trend. Nevertheless, these rising mortality rates require urgent interventions, including cancer prevention programs, increased access to medical services, and improved quality of life.

Globally, Gastric Cancer (GC) ranks as the fifth leading cause of cancer-related deaths. GC is a multifaceted malignancy with diverse etiologies; however, understanding the shared molecular mechanisms can aid in discovering novel targeted therapies for GC. This study has employed a drug repositioning approach to explore new drug candidates for treating GC.

The human GC cell lines AGS, MKN-45, and KATO-III were treated with different concentrations of dopamine, cabergoline, thioridazine, and entacapone to determine effective doses and IC50 values. In vitro, cytotoxic activity on cancer cell lines was screened based on dose/time using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) was used to measure the mRNA expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Proliferating Cell Nuclear Antigen (PCNA) in each group. The percentage of apoptotic cells was evaluated using Annexin V/PI staining.

Dopamine, cabergoline, thioridazine, and entacapone elicited cytotoxic effects on AGS and KATO-III cells in a dose-dependent manner and elevated the percentage of Annexin Vpositive cells, suggesting the occurrence of apoptosis. The expression of Bcl-2 and PCNA was significantly decreased, whereas the expression of Bax was considerably increased in the AGS and KATO-III cells compared to that in the blank group (p < 0.05); however, no similar effect was observed in MKN-45 cells.

Through in vitro experiments, this study provides evidence that the antipsychotic drugs cabergoline, dopamine, thioridazine, and entacapone can inhibit gastric cancer growth in AGS and KATO-III cells. These findings suggest that these drugs could be repurposed as novel therapeutic agents for the treatment of gastric cancer.

Background/Objectives: Gastric cancer is a leading cause of cancer-related mortality, particularly in East Asia, with a notable burden in Republic of Korea. This study aimed to construct and develop machine learning models for the prediction of gastric cancer mortality and the identification of risk factors. Methods: All data were acquired from the Korean Clinical Data Utilization for Research Excellence by multiple medical centers in South Korea. A total of 23,717 gastric cancer patients were divided into two groups by cause of mortality (all-cause of 2664 and disease-specific of 1620) and investigated. We used comprehensive data integrating clinical, pathological, lifestyle, and socio-economic factors. Cox proportional hazards analysis was conducted to estimate hazard ratios for mortality. Five machine learning models (random forest, gradient boosting machine, XGBoost, light GBM, and cat boosting) were developed to predict mortality. The models were interpreted by SHAP, one of the explainable AI techniques. Results: For all-cause mortality, the gradient-boosting machine learning model demonstrated the highest performance with an AUC-ROC of 0.795. For disease-specific mortality, the light GBM model outperformed others, achieving an AUC-ROC of 0.867. Significant predictors included the AJCC7 stage, tumor size, lymph node count, and lifestyle factors such as smoking, drinking, and diabetes. Conclusions: This study underscores the importance of integrating both clinical and lifestyle data to enhance mortality prediction accuracy in gastric cancer patients. The findings highlight the need for personalized treatment approaches in the Korean population and emphasize the role of demographic-specific data in predictive modeling.

Gastric cancer (GC) is a significant public health concern in the USA, and its burden is on the rise.

This study utilized the latest data from the Global Burden of Disease (GBD) study. We provided descriptive statistics on the incidence, prevalence, mortality, disability-adjusted life years (DALYs), and age-standardized rates (ASRs) of GC across the USA and states. By calculating percentage changes and average annual percentage changes (AAPC), along with conducting age-period-cohort analysis, we assessed the trends in the burden of GC. Decomposition analysis was then performed, followed by the application of an autoregressive integrated moving average (ARIMA) model to forecast changes in ASRs through 2036.

From 1990 to 2021, the number of incidence and prevalence of GC in the USA increased, but age-standardized incidence rates (ASIR) trended downward (AAPC = -0.73, 95% confidence interval [CI]: -0.77 to -0.68) and age-standardized prevalence rates (ASPR) (AAPC = -0.99, 95% CI: -1.08 to -0.9) showed a decreasing trend. In addition, the number of deaths, DALYs, age-standardized mortality rates (ASMR) and age-standardized DALYs rates (ASDR) in GC showed a decreasing trend. The burden of GC was significantly higher in males compared to females. In addition, we found that the highest incidence and prevalence in females was in the age group of 75-79 years, whereas the highest incidence and prevalence in males was in the age group of 70-74 years.

GC is a major public health issue in the USA. Although ASIR, ASPR, ASMR, and ASDR for GC are decreasing, the number of incidence and prevalence of GC in the USA remains high, and the disease burden of GC in the USA remains high. Strengthening preventive interventions, particularly for men and patients over the age of 60, will be crucial in the future.