Wen Dan Decoction (WDD) is primarily utilized as an "expectorant" in clinical practice. The combination of WDD and Lian Qiao (LQWDD) exhibits synergistic effects on phlegm resolution, qi regulation, and detoxification. In preliminary clinical practice, we observed that LQWDD effectively alleviates the severity of gastric precancerous lesions. Nevertheless, the underlying mechanism remains elusive.

This study was designed to explore the efficacy and potential mechanisms of LQWDD against gastric carcinogenesis.

Retrospective analyses of patients with gastric precancerous lesions and an N-methyl-N9-nitro-N-nitrosoguanidine (MNNG)-induced rat gastric cancer model were conducted to evaluate the efficacy of LQWDD against gastric carcinogenesis. Proteomic analyses were employed to investigate the underlying mechanisms of LQWDD. Moreover, energy metabolites were quantified using metabolomics. Network pharmacology and high-performance liquid chromatography-mass spectrometry were integrated to elucidate the potential active components of LQWDD. Additionally, seahorse analysis and RNA sequencing were used to explore the effects and underlying mechanisms of compound quercetin on oxidative phosphorylation.

LQWDD effectively impeded gastric carcinogenesis in an MNNG-induced rat gastric cancer model and patients. Proteomic analyses revealed that LQWDD protected the integrity of the oxidative phosphorylation pathway during gastric carcinogenesis, which was significantly suppressed in human gastric intraepithelial neoplasia and MNNG-induced gastric carcinoma. Moreover, LQWDD administration significantly reversed MNNG-induced reductions in the expression of mitochondrial complex I-related proteins (ALDH3A1 and NDUFS4), as well as in ATP, NAD+, and metabolite levels, indicating its protective role against oxidative phosphorylation dysfunction through the modulation of mitochondrial complex I-associated proteins. Furthermore, quercetin and kaempferol were identified as potential active components of LQWDD. These components suppressed the growth of gastric cancer cells and patient-derived organoids while simultaneously increasing intracellular ATP and NAD+ levels. Notably, quercetin exerted its preferential regulatory role in mitochondrial oxidative respiration by activating the AMPK signaling pathway.

Our study provides the first systematic evidence that mitochondrial OXPHOS dysfunction plays a pivotal role in gastric carcinogenesis. LQWDD and its potential active ingredient quercetin inhibit gastric carcinogenesis by mitigating oxidative phosphorylation impairment, highlighting on a promising therapeutic prescription for treating with gastric precancerous lesions.

As a traditional medicine and food homologous plant, Perilla frutescens is widely cultivated in China, Japan, and Korea. According to the Compendium of Materia Medica, the leaves, stems, and seeds of perilla can all be used as medicine. Perilla essential oil has been used in traditional Chinese medicine since ancient times. It has been demonstrated that perillaldehyde (PAH), a primary composition of the essential oil extracted from perilla, can inhibit tumor growth through multiple mechanisms. However, the specific mechanisms by which PAH suppresses gastric cancer remain incompletely understood.

We performed in vitro experiments using three cell lines (AGS, HGC27, and MFC) to assess the effects of PAH on cell viability, proliferation, and migration of gastric cancer cells. Concurrently, we established a subcutaneous gastric tumor model in BALB/c nude mice for in vivo animal studies. Subsequently, oxidative stress was measured via fluorescence staining techniques (H2DCFDA, DHE, and JC-1). We then evaluated whether PAH induced ferroptosis in gastric cancer cells through FerroOrange staining, quantification of intracellular glutathione (GSH) and lipid peroxidation levels, and Western blotting. Finally, PAH was co-administered with the ferroptosis inhibitor Ferrostatin-1 (Fer-1) or the ferroptosis inducer RSL3, and relevant experiments were re-evaluated.

In this study, PAH was proven to inhibit the growth of gastric cancer both in vivo and in vitro. It led to a reduction in mitochondrial membrane potential (MMP), an augmentation of the accumulation of reactive oxygen species (ROS), and an elevation of oxidative stress levels. Moreover, PAH decreased intracellular GSH levels while increasing intracellular lipid peroxidation and Fe2+ levels. These effects indicate that PAH induces ferroptosis via inhibiting the system Xc (-)/GSH/GPX4 axis. Furthermore, PAH influenced the expression of proteins related to iron transport and storage and regulated ferroptosis via the P62-Keap1-Nrf2 pathway. When combined with the ferroptosis inducer RSL3, PAH could promote ferroptosis in gastric cancer.

Our research suggests a potential therapeutic strategy in which PAH could be used to synergize with ferroptosis inducers for treating gastric cancer.

N6-methyladenosine (m6A) RNA methylation is crucially involved in the genesis and advancement of gastric cancer (GC) by controlling various pathobiological aspects including gene expression, signal transduction, metabolism, cell death, epithelial-mesenchymal transition, angiogenesis, and exosome function. Despite its importance, the exact mechanisms by which m6A modification influences GC biology remain inadequately explored. This review consolidates the latest advances in uncovering the mechanisms and diverse roles of m6A in GC and proposes new research and translational directions. Key regulators (writers, readers, and erasers) of m6A, such as METTL3/14/16 and WTAP, significantly affect cancer progression, anticancer immune response, and treatment outcomes. m6A modification also impacts immune cell infiltration and the tumor microenvironment, highlighting its potential as a diagnostic and prognostic marker. Interactions between m6A methylation and non-coding RNAs offer further novel insights into GC development and therapeutic targets. Targeting m6A regulators could enhance immunotherapy response, overcome treatment resistance, and improve oncological and clinical outcomes. Models based on m6A can precisely predict treatment response and prognosis in GC. Additional investigation is needed to fully understand the mechanisms of m6A methylation and its potential clinical applications and relevance (e.g., as precise markers for early detection, prediction of outcome, and response to therapy and as therapeutic targets) in GC. Future research should focus on in vivo studies, potential clinical trials, and the examination of m6A modification in other types of cancers.

Gastric cancer (GC) is one of the most common cancers worldwide particularly in Asian populations, and certain diets have been associated with increased risk of GC. Recent advances in microbial profiling technology have facilitated investigations on microbes residing on the gastric mucosa and increasing evidence has revealed the critical roles of non-Helicobacter pylori gastric microbes in gastric tumorigenesis. On the other hand, diets can affect microbial communities, causing compositional and functional shift of the microbiota. In this review, we summarize the influence of various diets including processed meat, salt-preserved food, high-fat diet, and alcohol on the development and progression of GC. We also explore microbial metabolites and host-microbe interactions in gastric tumorigenesis, alongside dietary interventions targeting the microbiota for the prevention and management against GC.

Background: Gastritis and duodenitis are highly prevalent upper gastrointestinal inflammatory conditions. We estimate the most up-to-date global, regional, and national burden in incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for gastritis and duodenitis from 1990 to 2021 with projections to 2050. Methods: Population-based data in this study was retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021). We evaluated the temporal trends of age-standardized rates of gastritis and duodenitis prevalence (ASPR), incidence (ASIR), mortality (ASMR), and DALYs (ASDR) across 204 countries and territories, as well as estimated annual percentage changes (EAPC) from 1990 to 2021. Analyses were stratified by sex, age subgroup, socio-demographic index (SDI) at the global, regional, and national level. A Bayesian age-period-cohort model was employed to project ASPR and ASDR of gastritis and duodenitis by sex and age up to 2050. Results: In 2021, 27.20 million (95% UI: 21.85-33.65) individuals globally had gastritis and duodenitis, with an ASIR of 323.24 (95% UI: 261.35-398.64) per 100,000. Globally, the prevalent cases of gastritis and duodenitis in 2021 was higher in females than in males and increased with age, peaking at the fifth decade of life. The number of prevalent cases of gastritis and duodenitis is projected to reach approximately 51.24 million by 2050. In 2021, gastritis and duodenitis caused 2.81 (95% UI: 2.17-3.61) million DALYs worldwide, with an ASDR of 35.64 (95% UI: 27.56-45.77) per 100,000, while the ASMR was 0.54 (95% UI: 0.47-0.62) per 100,000. Despite global decreases in ASPR and ASIR, increasing trends were observed in the low and low-middle SDI regions from 1990 to 2021. The low SDI regions exhibited the highest ASDR of 63.44 (95% UI: 44.08-87.16) per 100,000. Among 21 GBD regions, East Asia exhibited the highest ASPR and ASIR in 2021. The ASPR of gastritis and duodenitis in 2050 is forecast to be 402.14 per 100,000, with an ASDR of approximately 22.09 per 100,000. Conclusion: Despite global reductions in ASPR, ASIR, ASMR, and ASDR between 1990 and 2021, the global burden of gastritis and duodenitis exhibits regional disparities, closely linked to SDI levels. The highest burden of gastritis and duodenitis was observed in East Asia and Sub-Saharan Africa. More potent measures are urgently needed in low SDI regions to forestall the increase of Gastritis and duodenitis burden.

Diffuse-type gastric cancer (GC) is closely associated with genetic abnormalities; however, its exact pathological mechanisms are still not understood. It manifests without symptoms before advanced stages and is often difficult to diagnose using routine imaging tests. Therefore, specific targeted therapies for diffuse GC are currently unavailable. In this study, the extract of Pseudolysimachion pusanensis, which is endemic to Korea, inhibited the proliferation of GC cells, MKN1 and SNU668, while the other extracts of the two endemic Pseudolysimachion species did not show any activity. This led to the molecular networking analysis of Pseudolysimachion species to identify the molecules mostly observed only in P. pusanensis. Thirteen new (1-13) and eight known (14-21) compounds were obtained and structurally characterized. Of these, cucurbitacin derivative compounds 1 and 14-16 showed activity, and particularly, the IC50 value of compound 1 was 0.65 and 0.21 μM. Ki-67 expression analysis, single-cell originated cell proliferation assay, and western blot analysis of apoptotic cell death-related molecules revealed that compound 1 mediated both cytostasis and cellular death via apoptosis. Particularly, this compound exhibited an anti-tumorigenic effect on the invasion of diffuse-type GC cells by perturbing the epithelial-to-mesenchymal transition (EMT) pathway, as demonstrated by invasion assays using both 2D models and in vivo-like 3D spheroid co-culture models, as well as western blot analysis of EMT markers. In addition, some functional groups that may or may not be necessary for the activity of cucurbitacin derivatives were identified, and some clues that the presence of metal ions may affect the activity were provided.

Gastric cancer remains a major health challenge worldwide, with nearly 1 million new cases annually contributing to more than 650 000 deaths. Epidemiologically, gastric cancer shows substantial geographical variation in incidence, with higher rates in Asia, South America, and eastern Europe, and a rapid increase in early-onset cases among people younger than 50 years. Key risk factors for gastric cancer include Helicobacter pylori infection, diet, obesity, smoking, and genetic predisposition. Early detection through comprehensive diagnostic procedures is crucial for optimising treatment outcomes. Standard treatment approaches for locally advanced gastric cancer include surgical resection, particularly D2 lymphadenectomy, complemented by chemotherapy and radiotherapy. There is increasing implementation of minimally invasive surgical techniques for operable disease and integration of immune checkpoint inhibitors and targeted therapies for advanced stages. Emerging therapies, such as novel targeted treatments and next-generation immunotherapies, show promise in improving survival and quality of life. Future directions in the management of gastric cancer focus on precision medicine, continued advancement in immunotherapy, novel early detection methods, and a multidisciplinary approach to care. These strategies aim to enhance the overall effectiveness of treatment and prognosis worldwide.

The demonstration that Helicobacter pylori is a pathogenic bacterium with marked carcinogenic potential has paved the way for new preventive approaches for gastric cancer. Although decades of research have uncovered complex interactions of H. pylori with epithelial cells, current insights have refined our view on H. pylori-associated carcinogenesis. Specifically, the cell-type-specific effects on gastric stem and progenitor cells deep in gastric glands provide a new view on the ability of the bacteria to colonize long-term, manipulate host responses and promote gastric pathology. Furthermore, new, large-scale epidemiological data have shed light on factors that determine why only a subset of carriers progress to gastric cancer. Currently, technological advances have brought yet another revelation: H. pylori is far from the only microorganism able to colonize the stomach. Instead, the stomach is colonized by a diverse gastric microbiota, and there is emerging evidence for the occurrence and pathological effect of dysbiosis resulting from an aberrant interplay between H. pylori and the gastric mucosa. With the weight of this evidence mounting, here we consider how the lessons learned from H. pylori research inform and synergize with this emerging field to bring a more comprehensive understanding of the role of microbes in gastric carcinogenesis.

Ruthenium-based metallodrugs have garnered attention as a promising alternative for anticancer therapy, aiming to overcome chemoresistance and severe side effects linked to platinum-based drugs. However, ruthenium complexes tested in clinical trials to date have yielded unsatisfactory results. This study synthesized a positively charged ruthenium complex (Ru-2) that effectively penetrated cancer cells and exhibited superior cytotoxicity to cisplatin in vitro against cancer cell lines and organoids. Ru-2 selectively targeted mitochondria, disrupting their function by depolarizing mitochondrial membrane potential, elevating reactive oxygen species production, and impairing both oxidative phosphorylation and the tricarboxylic acid cycle. Furthermore, Ru-2 triggered endoplasmic reticulum (ER) stress and apoptosis. Integrative transcriptomic and proteomic analyses, performed using RNA sequencing and mass spectrometry, identified key molecular changes in cancer cells treated with Ru-2. For enhanced in vivo application, we developed a transferrin-based nanomedicine formulation, TF/Ru-2, incorporating Ru-2 into transferrin. In vivo studies demonstrated that both Ru-2 and TF/Ru-2 exhibited superior antitumor efficacy and improved biosafety compared to cisplatin. This study presents a novel ruthenium complex and a transferrin-based drug delivery platform with significant potential for future cancer therapies.

Gastric cancer (GC) represents a substantial public health challenge, characterized by elevated morbidity and mortality rates. Migrasomes, a newly discovered type of extracellular vesicle, have been highlighted as important contributors to cancer progression, though their specific role in GC remains unclear. To address this issue, we developed the first prognostic model utilizing migrasome-related long non-coding RNAs (MRLs). This model aims to deepen the understanding of GC pathogenesis and improve patient outcomes. Clinical and transcriptional data for 407 GC patients from TCGA were classified as training and testing sets. Through Pearson correlation analysis, 537 MRLs were recognized, and LASSO and Cox regression analyses further refined the list to four key lncRNAs (AC012055.1, LINC01150, AC053503.4, AC107021.2) for constructing the prognostic model. Kaplan-Meier survival analysis indicated a significantly poorer prognosis for the high-risk group. PCA confirmed the model's robustness, and univariate and multivariate analyses validated it as an independent predictor of clinical outcomes. The ROC curve and C-index evaluations further affirmed the model's predictive power. We developed a nomogram combining the MRLs signature with clinical parameters to enhance prognostic accuracy. GO, KEGG and GSEA were performed on migrasome-related genes associated with GC. Furthermore, high-risk patients exhibited increased immune cell infiltration and reduced tumor mutation burden, both associated with poorer outcomes. Additionally, twenty-nine potential therapeutic agents were identified. This novel MRLs-based model provides crucial insights into GC biology and represents a valuable tool for improving patient management and therapeutic strategies.

Chronic atrophic gastritis (CAG) is a prevalent chronic digestive disorder that, through sustained inflammation, can lead to severe mucosal damage and even gastric cancer. Current treatments offer limited efficacy, whereas Fu-Zheng-Huo-Wei Decoction (FZHWT), a traditional Chinese medicine (TCM) formulation, shows promising potential in treating CAG.

This study aims to identify the key active components of FZHWT and evaluate its therapeutic effects on CAG.

UPLC-MS/MS was used to identify the bioactive compounds in FZHWT. A CAG rat model was established to assess its therapeutic effects, and transcriptome sequencing was conducted to identify key targets and mechanisms. A CAG cell model was used for validation of the transcriptomic findings, and histological techniques and molecular biology methods were employed for further validation.

A total of 1362 chemical components were identified in FZHWT, of which 25 are bioavailable compounds. Differential metabolite analysis revealed four key active ingredients: Nicotiflorin, Stachydrine, 5-O-p-Coumaroylquinic acid, and N-(4-oxopentyl)-acetamide. In the CAG rat model, FZHWT significantly reduced inflammation and gastric mucosal damage. Transcriptome sequencing highlighted Sema5a as a key target and revealed the involvement of several inflammatory signaling pathways. In the CAG cell model, FZHWT alleviated CAG by inhibiting inflammation and promoting gastric mucosal repair.

FZHWT demonstrates significant therapeutic potential in treating CAG by modulating inflammatory pathways and promoting mucosal repair. This study provides new insights into the treatment of CAG and supports the modernization of multi-component TCM formulas.

Currently, gastric cancer treatment remains an enormous challenge and requires a multidisciplinary approach. Globally, the incidence and prevalence of gastric cancer vary, with the highest rates found in East Asia, Central Europe, and Eastern Europe. Early diagnosis is critical for successful surgical removal of gastric cancer, but the disease often develops asymptomatically. Therefore, many cases are diagnosed at an advanced stage, resulting in poor survival. Metastatic gastric cancer also has a poor prognosis. Therefore, it is urgent to identify reliable molecular disease markers and develop an effective medical treatment for advanced stages of the disease. This review summarizes potential prognostic or predictive markers of gastric cancer. Furthermore, the role of tryptophan metabolites from the kynurenine pathway as prognostic, predictive, and diagnostic factors of gastric cancer is discussed, as this metabolic pathway is associated with tumor immune resistance.

Gastric cancer remains a leading cause of cancer-related mortality worldwide. In the United States, gastric cancer incidence and mortality are substantially higher among non-White racial and ethnic groups and new immigrants from high-incidence countries. This is in large part related to the higher prevalence of Helicobacter pylori -associated gastric premalignant changes in these populations. Apart from primary prevention, early detection of gastric cancer is the principal strategy to reduce gastric cancer mortality and improve survival. Extensive evidence in Asian countries has demonstrated the benefits of endoscopic screening in detecting early-stage gastric cancer and reducing gastric cancer-related mortality. By contrast, direct, high-quality US-based data, such as from large clinical trials or observational studies, on important outcomes of gastric cancer screening are still lacking. In this review, we evaluate and summarize the latest global evidence on the epidemiology and predisposing factors of gastric cancer as well as the efficacy, benefits vs. risks, and cost-effectiveness of gastric cancer screening. We further discuss the critical knowledge gaps and challenges in promoting gastric cancer screening in the United States. Dedicated research is urgently needed to enrich the US-based data on gastric cancer primary and secondary prevention to inform clinical practice and reduce gastric cancer-related morbidity and mortality in a cost and resource efficient manner.

Lymph node status is a critical prognostic factor in gastric cancer (GC), but stage migration may occur in pathological lymph nodes (pN) staging. To address this, alternative staging systems such as the positive lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) were introduced.

To assess the prognostic accuracy and stratification efficacy of three nodal staging systems in GC.

A systematic review identified 12 studies, from which hazard ratios (HRs) for overall survival (OS) were summarized. Sensitivity analyses, subgroup analyses, publication bias assessments, and quality evaluations were conducted. To enhance comparability, data from studies with identical cutoff values for pN, LNR, and LODDS were pooled. Homogeneous stratification was then applied to generate Kaplan-Meier (KM) survival curves, assessing the stratification efficacy of three staging systems.

The HRs and 95% confidence intervals for pN, LNR, and LODDS were 2.16 (1.72-2.73), 2.05 (1.65-2.55), and 3.15 (2.15-4.37), respectively, confirming all three as independent prognostic risk factors for OS. Comparative analysis of HRs demonstrated that LODDS had superior prognostic predictive power over LNR and pN. KM curves for pN (N0, N1, N2, N3a, N3b), LNR (0.1/0.2/0.5), and LODDS (-1.5/-1.0/-0.5/0) revealed significant differences (P < 0.001) among all prognostic stratifications. Mean differences and standard deviations in 60-month relative survival were 27.93% ± 0.29%, 41.70% ± 0.30%, and 26.60% ± 0.28% for pN, LNR, and LODDS, respectively.

All three staging systems are independent prognostic factors for OS. LODDS demonstrated the highest specificity, making it especially useful for predicting outcomes, while pN was the most effective in homogeneous stratification, offering better patient differentiation. These findings highlight the complementary roles of LODDS and pN in enhancing prognostic accuracy and stratification.

This study investigates the extraction of partially purified sulphated polysaccharides from marine bivalves through enzymatic digestion followed by sequential deproteinization and evaluates their anti-gastric cancer activity. Chemical analysis confirmed high uronic acid and sulfate content, with FT-IR validating characteristic functional groups. Donax variabilis polysaccharide demonstrated significant, dose-dependent anti-proliferative effects against AGS cells. Mechanistic studies revealed morphological changes, ROS generation, LDH release, and mitochondrial membrane disruption, leading to apoptosis. Flow cytometry confirmed G0/G1 phase arrest. These findings suggest that D. variabilis sulphated polysaccharides exhibit potent anti-gastric cancer properties, likely through oxidative stress and mitochondrial dysfunction, warranting further investigation for therapeutic applications.

To identify key cellular changes and molecular events in atrophic mucosa, we aimed to elucidate the molecular mechanisms driving the occurrence of chronic atrophic gastritis (CAG).

We used single-cell RNA sequencing (scRNA-seq) to characterize changes in the epithelial state and tissue microenvironment associated with CAG. The molecular changes were identified by comparing differentially expressed genes (DEGs) between the two mucosa states. Gene Ontology (GO) pathway enrichment analysis was used to explore the potential functional changes in each cell subtype in atrophic mucosa. Gene set score analysis was conducted to compare the functional roles of different fibroblast subtypes and functional changes in cell subtypes between the CAG and control groups. Metabolic analysis was performed to compare the metabolic activity of C1Q+ macrophages under different conditions. NichNet analysis was used to analyze the regulatory relationships between CCL11+APOE+ fibroblasts and C1Q+ macrophages and between CCL11+APOE+ fibroblasts and CD8+ effector T cells. Transcription factor (TF) analysis was performed to determine the transcription status of different T-cell subtypes in atrophic and normal mucosa.

We generated a single-cell transcriptomic atlas from 3 CAG biopsy samples and paired adjacent normal tissues. Our analysis revealed that chief cells and parietal cells exhibited a loss of detoxification ability and that surface mucous cells displayed a reduced antimicrobial defense ability in CAG lesions. The mucous neck cells in CAG lesions showed upregulation of genes related to cell cycle transition, which may lead to aberrant DNA replication. Additionally, cells with the T exhaustion phenotype infiltrated under CAG condition. C1Q+ macrophages exhibited reduced phagocytosis, downregulated expression of pattern recognition receptors and decreased metabolic activity. NichNet analysis revealed that a subpopulation of CXCL11+APOE+ fibroblasts regulated the inflammatory response in the pathogenesis of atrophic gastritis. APSN+CXCL11+APOE+ fibroblasts were found to be associated with gastric cancer (GC) development.

The main goal of this study was to comprehensively elucidate the cellular changes in CAG lesions. We observed an immune decline in the mucosal microenvironment during the development of CAG, including a reduced immune response of C1Q+ macrophages, reduced cytotoxicity of T cells, and increased infiltration of exhausted T cells. Specifically, we demonstrated that different epithelial subtypes aberrantly express genes related to susceptibility to external bacterial infection and aberrant cell cycle progression. Our study provides new insights into the functions of epithelial changes and immune alterations during the development of CAG.

Gastric cancer (GC) is a significant worldwide health concern and is a leading cause of cancer-related mortality. Immunotherapy has arisen as a promising strategy to stimulate the patient's immune system in combating cancer cells. Nevertheless, the effectiveness of immunotherapy in individuals with gastric cancer (GC) is not yet optimal. Thus, it is crucial to discover biomarkers capable appof predicting the advantages of immunotherapy for tailored treatment. The tumor microenvironment (TME) and its constituents, including cancer-associated fibroblasts (CAFs), exert a substantial influence on immune responses and treatment outcomes. In this investigation, we utilized single-cell RNA sequencing to profile CAFs in GC and established a scoring method, referred to as the CAF score (CAFS), for the prediction of patient prognosis and response to immunotherapy. Through our analysis, we successfully identified distinct subgroups within CAFs based on CAF score (CAFS), namely CAFS-high and CAFS-low subgroups. Notably, we noted that individuals within the CAFS-high subgroup experienced a lessF favorable prognosis and displayed diminished responsiveness to immunotherapy in contrast to the CAFS low subgroup. Furthermore, we analyzed the mutation and immune characteristics of these subgroups, identifying differentially mutated genes and immune cell compositions. We established that CAFS could forecast treatment advantages in patients with gastric cancer, both for chemotherapy and immunotherapy. Its efficacy was additionally confirmed in contrast to other biomarkers, including Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenotypic Score (IPS). These findings emphasize the clinical relevance and potential utility of CAFS in guiding personalized treatment strategies for gastric cancer.

Gastric cancer (GC) stands as one of the most formidable malignancies worldwide. It is well-established that miRNAs play a crucial role in the initiation and progression of various human cancers. Among these, miR-99a-3p has been implicated in the pathogenesis of GC. In the context of our study, we embarked on the comprehensive examination of miR-99a-3p expression in GC cells. Additionally, we sought to establish a correlation between miR-99a-3p expression levels and the overall survival (OS) of GC patients, and our findings hinted at its potential role in predicting an unfavorable prognosis. To further investigate the functional implications of miR-99a-3p in GC, we conducted a series of cell-based experiments after successfully knocking down miR-99a-3p. These investigations uncovered a substantial inhibition of cellular events associated with tumor progression. Moreover, employing TargetScan, we identified Tripartite motif-containing protein 21 (TRIM21) as a putative target with a binding site for miR-99a-3p. Subsequent dual-luciferase reporter gene assay confirmed the direct interaction between miR-99a-3p and TRIM21. Western blot analysis validated the alteration in TRIM21 expression levels, revealing an upregulation upon miR-99a-3p knockdown. Building on these molecular findings, we extended our investigations to human GC tissues, where we observed a downregulation of TRIM21, which, notably, correlated with shorter overall survival. Lastly, to further solidify our conclusions, we conducted a series of in vitro and in vivo rescue experiments, collectively suggesting that miR-99a-3p promoted the progression of GC cells through the downregulation of TRIM21. In summary, our study comprehensively explored the role of miR-99a-3p in GC, revealing its association with unfavorable patient outcomes, functional implications in tumor progression, and a direct regulatory relationship with TRIM21. These findings collectively underscore the significance of miR-99a-3p in the pathogenesis of GC and present a potential therapeutic avenue for further investigation.

Gastric cancer (GC) is a major health concern worldwide. One important contributing factor is the presence of the Epstein-Barr virus (EBV). However, the molecular pattern of how EBV participates in the malignant transition process remains unclear.

GC samples were stained by immunohistochemistry, fluorescent and EBV-encoded small RNA in situ hybridization to identify CD8 expression, CDKN2A genomic alteration, and EBV existence. Functional potentials of EBV infection were predicted by bioinformatic enrichment analysis.

CDKN2A genestayed intact in all EBV-associated GC cases. Meanwhile, CDKN2A deletion (8.43% cases) was exclusive to EBV-negative GC cases. Furthermore, EBV infection was positively correlated with CD8+T cell infiltration, and both of them predicted better prognosis.

This study highlighted the comprehensive impact of EBV infection in GC formation and proposed a thought-provoking observation for further investigation into the roles of CDKN2A and EBV infection in gastric tumorigenesis.

Cancer remains one of the leading causes of mortality worldwide, characterized by uncontrolled cell growth and the ability of tumors to invade surrounding tissues and spread to distant organs. Despite significant advancements in early detection, diagnosis, and treatment, many cancers still present substantial challenges due to their heterogeneity, resistance to conventional therapies, and severe side effects of existing treatments. Consequently, there is an ongoing need for novel therapeutic agents to selectively target cancer cells, enhance the efficacy of current treatments, and minimize adverse effects. Isoorientin (ISO) is a naturally occurring flavonoid known for its anticancer properties. ISO has demonstrated the ability to influence several critical processes in cancer progression, such as cell proliferation, apoptosis, and metastasis. Due to the absence of clinical trials, we included only in vitro studies, reviewing 13 investigations. These studies covered diverse cancer types, including lung, brain, oral, liver, pancreatic, and gastric cancers, and assessed various outcomes related to cell viability, apoptosis, migration, and molecular pathway modulation. By synthesizing data from these investigations, our review seeks to provide a thorough understanding of ISO's anticancer effects, its mechanisms of action, and its potential as a therapeutic agent.

Disorders, including cancer, metabolic disorders, and neurodegenerative diseases, can threaten human health; therefore, disease prevention is essential. Naringenin, a phytochemical with low toxicity, has been used in various disease prevention studies. This study aimed to comprehensively review the effects of naringenin on human health. First, we introduced the general characteristics of naringenin and its pharmacokinetic features when absorbed in the body. Next, we summarized the inhibitory effects of naringenin on colorectal, gastric, lung, breast, ovarian, cervical, prostate, bladder, liver, pancreatic, and skin cancers in preclinical studies. Lastly, we investigated the inhibitory effects of naringenin on metabolic disorders, including diabetes, obesity, hyperlipidemia, hypertension, cardiac toxicity, hypertrophy, steatosis, liver disease, and arteriosclerosis, as well as on neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In conclusion, naringenin may serve as a significant natural compound that benefits human health.

Gastric cancer remains a significant global health challenge, causing a substantial number of cancer-related deaths, particularly in China. While the exact causes of gastric cancer are still being investigated, Helicobacter pylori (H. pylori) infection has been identified as the primary risk factor, which triggers chronic inflammation and a multistage progression of gastric lesions that may lead to carcinogenesis over a long latency time. Since the 1990s, numerous efforts have focused on assessing the effectiveness of H. pylori eradication in preventing new cases of gastric cancer among both the general population and patients who have undergone early-stage cancer treatment. This body of work, including several community-based interventions and meta-analyses, has shown a reduction in both the incidence of and mortality from gastric cancer following H. pylori treatment, alongside a decreased risk of metachronous gastric cancer. In this review, we seek to consolidate current knowledge on the effects of H. pylori treatment on gastric cancer prevention, its systemic consequences, cost-effectiveness, and the influence of antibiotic resistance and host characteristics on treatment outcomes. We further discuss the potential for precision primary prevention of H. pylori treatment and comment on the efficient implementation of test-and-treat policies and allocation of health resources towards minimizing the burden of gastric cancer globally.

Jianwei Xiaoyan Granule (JWXYG) is the traditional Chinese medicine preparation in Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, which has been widely used in clinical treatment of chronic atrophic gastritis (CAG). However, the material basis and potential mechanism of JWXYG in the treatment of CAG are not clear.

To explore the material basis and potential mechanism of JWXYG in the treatment of CAG.

In this study, the components of JWXYG were analyzed by HPLC-Q-TOF-MS/MS. Then, the CAG model in rats established by a composite modeling method and MC cell model induced by MNNG were used to explore the improvement effect of JWXYG on CAG. Finally, the potential mechanism of JWXYG in the treatment of CAG was preliminarily predicted based on network pharmacology and validated experimentally.

Thirty-one components of JWXYG were analyzed through HPLC-Q-TOF-MS/MS, such as albiflorin, paeoniflorin, lobetyolin firstly. Research results in vivo showed that the gastric mucosa became thinner, intestinal metaplasia appeared, the number of glands was reduced, the serum levels of PG I and PG II increased and the contents of G17 and IL-6 reduced in CAG model rats. After 4 weeks of JWXYG (2.70 g/kg) administration, these conditions were significantly improved. In addition, cell viability, migration, and invasion of MNNG-induced MC cells was inhibited by JWXYG treatment (800 μg/mL). Furthermore, the results of network pharmacology indicated that HIF-1 and VEGF signaling pathways might play important roles in the therapeutic process. Then the results of Western blot, immunohistochemistry and immunofluorescence confirmed that with JWXYG treatment, the increased expression of HIF-1α, VEGF and VEGFR2 in gastric issue of CAG rats were restrained. Eventually, potential components of JWXYG in the treatment of CAG were predicted through molecular docking to elucidate the material basis.

JWXYG could inhibit angiogenesis by regulating HIF-1α-VEGF pathway to exert therapeutic effects on CAG. Our study explored the potential mechanisms and material basis of JWXYG in the treatment of CAG and provides experimental data for the clinical rational application of JWXYG.

The progression of gastric cancer involves a complex multi-stage process, with gastroscopy and biopsy being the standard procedures for diagnosing gastric diseases. This study introduces an innovative non-invasive approach to differentiate gastric disease stage using gastric fluid samples through machine-learning-assisted surface-enhanced Raman spectroscopy (SERS). This method effectively identifies different stages of gastric lesions. The XGBoost algorithm demonstrates the highest accuracy of 96.88% and 91.67%, respectively, in distinguishing chronic non-atrophic gastritis from intestinal metaplasia and different subtypes of gastritis (mild, moderate, and severe). Through blinded testing validation, the model can achieve more than 80% accuracy. These findings offer new possibilities for rapid, cost-effective, and minimally invasive diagnosis of gastric diseases.

Comprehensive treatment of gastric cancer (GC) is progressing, but the rapid proliferation and metastasis of GC remains a cause of high recurrence and mortality rates. In this study we investigated GC-associated circRNA tending to yield more insight into the mechanisms of gastric cancer development.

We detected the expression levels of circTSN in GC tissues and cell lines using qRT-PCR. The circular structure of circTSN was confirmed by Sanger sequencing, agarose gel electrophoresis and RNase R. A series of cell functional experiments were employed to investigate the implication of circTSN aberrant expression on the proliferation and metastasis of GC cells. The predicted binding domain between circTSN and miR-1825 was analyzed by luciferase reporter gene analysis. Meanwhile, subcutaneous tumor xenografts in nude mice were used to validate the role of circTSN in vivo.

It was found that RNA levels of circTSN were significantly elevated in GC tissues and cell lines, which was also confirmed to contain a closed-loop structure. CCK8, clone formation, EdU, transwell and in vivo experiments indicated that the highly expressed circTSN was involved in the proliferation and metastasis process of GC. In addition, circTSN modulates the expression of SLC38A2 by sequence-specific binding to miR-1825.

This study identified that circTSN, which is highly expressed in GC, was able to contribute to the proliferation and metastasis of GC cell through miR-1825/SLC38A2 axis and this might provide a new candidate target for the precision treatment of GC.

Background: The prognosis of patients diagnosed with locally advanced and metastatic gastric and esophago-gastric junction cancer is critical. The optimal choice of systemic therapy is essential to optimize survival outcomes. Methods: A comprehensive literature review via PubMed and analysis of major oncology congresses (European Society for Medical Oncology and American Society of Clinical Oncology websites) were conducted to ascertain the current status and latest developments in the systemic treatment of patients with localized or advanced gastric and esophago-gastric junction adenocarcinoma. Results: While neoadjuvant and perioperative chemotherapy for localized tumor stages is the preferred approach in the Western Hemisphere, adjuvant chemotherapy remains the preferred course of action in East Asia. The administration of chemotherapy, typically in the form of combinations comprising platinum and fluoropyrimidine compounds in combination with docetaxel, represents a standard of care. Investigations are underway into the potential of immunotherapy and other biologically targeted agents in the perioperative setting. To select the most appropriate therapy for advanced gastric cancer, including adenocarcinoma of the esophago-gastric junction, it is essential to determine biomarkers such as HER2 expression, PD-L1 combined positive score (CPS) (combined positive score), Claudin 18.2, and microsatellite instability (MSI). In the present clinical context, the standard first-line therapy is a combination of fluoropyrimidine and a platinum derivative. The selection of chemotherapy in combination with antibodies is contingent upon the specific biomarker under consideration. Conclusions: This article reviews the current state of the art based on recent clinical trial results and provides an outlook on the future of systemic therapy.

Gastric cancer (GC) is the second most common cause of cancer-related death worldwide and a serious public health concern. This high death rate is mostly caused by late-stage diagnoses, which lead to poor treatment outcomes. Radiation immunotherapy and targeted therapies are becoming increasingly popular in GC treatment, in addition to surgery and systemic chemotherapy. In this review, we have focused on both in vitro and in vivo research, which presents a summary of recent developments in targeted therapies for gastric cancer. We explore targeted therapy approaches, including integrin receptors, HER2, Claudin 18, and glutathione-responsive systems. For instance, therapies targeting the integrin receptors such as the αvβ3 and αvβ5 integrins have shown promise in enhancing diagnostic precision and treatment efficacy. Furthermore, nanotechnology provides novel approaches to targeted drug delivery and imaging. These include glutathione-responsive nanoplatforms and cyclic RGD peptide-conjugated nanoparticles. These novel strategies seek to reduce systemic toxicity while increasing specificity and efficacy. To sum up, the review addresses the significance of personalized medicine and advancements in gastric cancer-targeted therapies. It explores potential methods for enhancing gastric cancer prognosis and treatment in the future.

The oncogenic role of long intergenic noncoding RNA for IGF2BP2 stability (LINRIS) has been reported in colorectal cancer. This research aimed to study its potential involvement in gastric cancer (GC). In this study, paired GC and non-tumor tissues were obtained from 64 GC patients, and the levels of LINRIS, mature microRNA-34a (miR-34a), and miR-34a precursor in these tissues were measured with RT-qPCR. Linear regression was used to analyze their correlations. The role of LINRIS overexpression and siRNA silencing in regulating the maturation of miR-34a was analyzed by RT-qPCR. Cell apoptosis was studied with flow cytometry. It was observed that LINRIS was overexpressed in GC and showed a negative correlation with mature miR-34a, but not miR-34a precursor. In GC cells, LINRIS siRNA silencing upregulated mature miR-34a level, but not miR-34a precursor level. LINRIS overexpression downregulated miR-34a level. Cell apoptosis analysis showed that LINRIS siRNA silencing and miR-34a overexpression promoted GC cell apoptosis and suppressed cell migration and invasion, while LINRIS overexpression suppressed cell apoptosis and enhanced cell migration and invasion. In addition, the effect of LINRIS overexpression was reversed by miR-34a overexpression. Therefore, LINRIS siRNA silencing in GC may promote cell apoptosis by promoting miR-34a maturation.

Early screening is crucial for the prevention of intestinal-type gastric cancer. The objective of the current study was to ascertain molecular evolution of intestinal-type gastric cancer according to the Correa cascade for the precise gastric cancer screening. We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection-resected specimens from 14 Chinese patients by microdissection, and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using the whole exome sequencing, identifying multiple variants at different Correa stages. The results showed that TP53, PCLO, and PRKDC were the most frequently mutated genes in the early gastric cancer (EGC). A high frequency of TP53 alterations was found in low-grade intraepithelial neoplasia (LGIN), which further increased in high-grade intraepithelial neoplasia (HGIN) and EGC. Intestinal metaplasia (IM) had no significant correlation with EGC in terms of mutational spectra, whereas both LGIN and HGIN showed higher genomic similarities to EGC, compared with IM. Based on Jaccard similarity coefficients, three evolutionary models were further constructed, and most patients showed linear progression from LGIN to HGIN, ultimately resulting in EGC. The ECM-receptor interaction pathway was revealed to be involved in the linear evolution. Additionally, the retrospective validation study of 39 patients diagnosed with LGIN indicated that PRKDC mutations, in addition to TP53 mutations, may drive LGIN progression to HGIN or EGC. In conclusion, the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer, elucidates the underlying molecular mechanisms of gastric carcinogenesis, and provides some evidence for potential personalized gastric cancer surveillance.

Precancerous lesions typically precede gastric cancer (GC), but the molecular mechanisms underlying the transition from these lesions to GC remain unclear. Therefore, it is urgent to understand this transition from precancerous lesions to GC, which is crucial for the early diagnosis and treatment of GC. In this study, we merged multiple single-cell RNA sequencing datasets to investigate the molecular changes in distinct cell types associated with the progression of GC. First, we observed an increasing abundance of immune cells and a decrease in non-immune cells from non-atrophic gastritis to GC. Five immune cell types were significantly enriched in GC compared to precancerous lesions. Moreover, we found that the interleukin (IL)-17 signaling pathway and Th17 cell differentiation were significantly up-regulated in immune cell subsets during GC progression. Some genes in these processes were predominantly expressed at the GC stage, highlighting their potential as diagnostic markers. Furthermore, we validated our findings using bulk RNA sequencing data from The Cancer Genome Atlas and confirmed consistent immune cell changes during GC progression. Our study provides insights into the immune infiltration and signaling pathways involved in the development of GC, contributing to the development of early diagnosis and targeted treatment strategies for this malignancy.

Gastric adenocarcinoma (GA) is a heterogeneous malignancy with high invasion and metastasis. We aimed to explore the metastatic characteristics of GA using single-cell RNA-sequencing (scRNA-seq) analysis.

The scRNA-seq dataset was downloaded from the GEO database and the "Seurat" package was used to perform the scRNA-seq analysis. The CellMarker2.0 database provided gene markers. Subsequently, differentially expressed genes (DEGs) were identified using the FindMarkers function and subjected to enrichment analysis with the "ClusterProlifer". "GseaVis" package was used for visualizing the gene levels. Finally, the SCENIC analysis was performed for identifying key regulons. The expression level and functionality of the key genes were verified by quantitative real-time PCR (qRT-PCR), wound healing and transwell assays.

A total of 7697 cells were divided into 8 cell subsets, in which the Cytotoxic NK/T cells, Myeloid cells and Myofibroblasts had higher proportion in the metastatic tissues. Further screening of DEGs and enrichment analysis revealed that in the metastatic tissues, NK cells, monocytes and inflammatory fibroblasts with low immune levels contributed to GA metastasis. In addition, this study identified a series of key immune-related regulons that mediated the lower immune activity of immune cells. Further in vitro experiment verified that CXCL8 was a key factor mediating the proliferation and migration of GA cells.

The scRNA-seq analysis showed that high infiltration of immune cells with lower immune activity mediated heterogeneity to contribute to GA metastasis.

Gastric cancer (GC) is a highly heterogeneous disease with a complex tumor microenvironment (TME) that encompasses multiple cell types including cancer cells, immune cells, stromal cells, and so on. Cancer-associated cells could remodel the TME and influence the progression of GC and therapeutic response. Single-cell RNA sequencing (scRNA-seq), as an emerging technology, has provided unprecedented insights into the complicated biological composition and characteristics of TME at the molecular, cellular, and immunological resolutions, offering a new idea for GC studies. In this review, we discuss the novel findings from scRNA-seq datasets revealing the origin and evolution of GC, and scRNA-seq is a powerful tool for investigating transcriptional dynamics and intratumor heterogeneity (ITH) in GC. Meanwhile, we demonstrate that the vital immune cells within TME, including T cells, B cells, macrophages, and stromal cells, play an important role in the disease progression. Additionally, we also overview that how scRNA-seq facilitates our understanding about the effects on individualized therapy of GC patients. Spatial transcriptomes (ST) have been designed to determine spatial distribution and capture local intercellular communication networks, enabling a further understanding of the relationship between the spatial background of a particular cell and its functions. In summary, scRNA-seq and other single-cell technologies provide a valuable perspective for molecular and pathological disease characteristics and hold promise for advancing basic research and clinical practice in GC.

Paired immunoglobin-like type 2 receptor beta (PILRB) mainly plays a crucial role in regulating innate immunity, but whether PILRB is involved in cancer is poorly understood. Here, we report that PILRB potentiates the PI3K/AKT pathway to drive gastric tumorigenesis by binding and stabilizing IRS4, which could hyperactivate the PI3K/AKT pathway. Firstly, the levels of PILRB are upregulated in human gastric cancer (GC) specimens and associated with poor prognosis in patients with GC. In addition, our data show that PILRB promotes cell proliferation, colony formation, cell migration and invasion in GC cells in vitro and in vivo. Mechanistically, PILRB recruits the deubiquitination enzymes OTUB1 to IRS4 and relieves K48-linked ubiquitination of IRS4, protecting IRS4 protein from proteasomal-mediated degradation and subsequent activation of the PI3K/AKT pathway. Importantly, the levels of PILRB are positively correlated with IRS4 in GC specimens. Meanwhile, we also found that PILRB reprogrammed cholesterol metabolism by altering ABCA1 and SCARB1 expression levels, and PILRB-expression confers GC cell resistance to statin treatment. Taken together, our findings illustrate that the oncogenic role of PILRB in gastric tumorigenesis, providing new insights into the regulation of PI3K/AKT signaling in GC and establishing PILRB as a biomarker for simvastatin therapy resistance in GC.

Although rare, there is ongoing research into biomarkers that predict the onset and recurrence of gastric cancer, particularly focusing on substances found in exosomes. Long non-coding RNAs (lncRNAs) have garnered attention for their potential in diagnosing gastric cancer. This study investigates the role of lncRNAs in gastric cancer, focusing on their presence in exosomes as potential biomarkers for the disease's onset and recurrence. We utilized the ArrayStar Human LncRNA array 2.0 to analyze lncRNA expression in tissues from early-stage gastric cancer patients. Our analysis highlighted LINC00853, which was significantly upregulated in cancer tissues and implicated in promoting epithelial-mesenchymal transition via the MAP17/PDZK1/AKT pathway. Functional studies on AGS and MKN74 gastric cancer cell lines demonstrated that LINC00853 facilitates cell proliferation, invasion, and migration. Additionally, RNA immunoprecipitation and electrophoretic mobility shift assays confirmed LINC00853 interaction with MAP17. Importantly, LINC00853 was also detected in exosomes from both patient samples and cell lines, and its downregulation led to decreased tumorigenicity in AGS cells. These findings suggest that both cellular and exosomal LINC00853 contribute to gastric cancer pathogenesis and may serve as valuable biomarkers for the disease.

Gastric cancer (GC) poses a significant global health challenge. This study is aimed at elucidating the role of the immune system, particularly T cells and their subtypes, in the pathogenesis and progression of intestinal-type gastric carcinoma (GC), and at evaluating the predictive utility of a T cell marker gene-based risk score for overall survival.

We performed an extensive analysis using single-cell RNA sequencing data to map the diversity of immune cells and identify specific T cell marker genes within GC. Pseudotime trajectory analysis was employed to observe the expression patterns of tumor-related pathways and transcription factors (TFs) at various disease stages. We developed a risk score using data from The Cancer Genome Atlas (TCGA) as a training set and validated it with the GSE15459 dataset.

Our analysis revealed distinct patterns of T cell marker gene expression associated with different stages of GC. The risk score, based on these markers, successfully stratified patients into high-risk and low-risk groups with significantly different overall survival prospects. High-risk patients exhibited poorer survival outcomes compared to low-risk patients (p < 0.05). Additionally, the risk score was capable of identifying patients across a spectrum from chronic atrophic gastritis to early GC.

The findings enhance the understanding of the tumor immune microenvironment in GC and propose new immunotherapeutic targets. The T cell marker gene-based risk score offers a potential tool for gastroenterologists to tailor treatment plans more precisely according to the cancer's severity.

Despite a radical operation, about half of gastric cancer (GC) patients with advanced GC experience peritoneal metastasis (PM), and the patients with PM have a poor prognosis. However, because staging laparoscopy was a highly invasive procedure for patients, identification of PM using a liquid biopsy can be useful for patients with GC.

This study analyzed two genome-wide miRNA expression profiling datasets (GSE164174 and TCGA). The study prioritized biomarkers in pretreatment plasma specimens from clinical training and validation cohorts of patients with GC. The authors developed an integrated exosomal miRNA panel and established a risk-stratification model, which was combined with the miRNA panel and currently used tumor markers (CEA, CA19-9, CA125, and CA72-4 levels).

The comprehensive discovery effort identified a four-miRNA panel that robustly predicted the metastasis with excellent accuracy in the TCGA dataset (area under the curve [AUC] 0.86). A circulating exosomal miRNA panel was established successfully with remarkable diagnostic accuracy in the clinical training (AUC 0.85) and validation (AUC 0.86) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to that of conventional clinical factors (P < 0.01), and the risk-stratification model was dramatically superior to the panel and currently used clinical factors for predicting PM (AUC 0.94; univariate: odds ratio [OR] 77.00 [P < 0.01]; multivariate OR 57.71 [P = 0.01]).

The novel risk-stratification model for predicting PM has potential for clinical translation as a liquid biopsy assay for patients with GC. The study findings highlight the potential clinical impact of the model for improved selection and management of patients with GC.

Gastric cancer (GC) is a refractory malignant tumor with high tumor heterogeneity, a low rate of early diagnosis, and poor patient prognosis. Lipid metabolism reprogramming plays a critical role in tumorigenesis and progression, but its prognostic role and regulatory mechanism in GC are rarely studied. Thus, the identification of signatures related to lipid metabolism is necessary and may present a new avenue for improving the overall prognosis of GC.

Lipid metabolism-associated genes (LMAGs) with differential expression in tumor and tumor-adjacent tissue were acquired to identify lipid metabolism-associated subtypes. The differentially expressed genes (DEGs) between the two clusters were then utilized for prognostic analysis and signature construction. Additionally, pathway enrichment analysis and immune cell infiltration analysis were employed to identify the characteristics of the prognostic model. Further analyses were conducted at the single-cell level to better understand the model's prognostic mechanism. Finally, the prediction of immunotherapy response was used to suggest potential treatments.

Two lipid metabolism-associated subtypes were identified and 9 prognosis-related genes from the DEGs between the two clusters were collected for the construction of the prognostic model named lipid metabolism-associated signature (LMAS). Then we found the low LMAS patients with favorable prognoses were more sensitive to ferroptosis in the Cancer Genome Atlas of Stomach Adenocarcinoma (TCGA-STAD). Meanwhile, the tumor cells exhibiting high levels of lipid peroxidation and accumulation of reactive oxygen species (ROS) in single-cell levels were primarily enriched in the low LMAS group, which was more likely to induce ferroptosis. In addition, endothelial cells and cancer-associated fibroblasts (CAFs) facilitated tumor angiogenesis, proliferation, invasion, and metastasis through endothelial-mesenchymal transition (EndMT), affecting the prognosis of the patients with high LMAS scores. Moreover, CD1C- CD141- dendritic cells (DCs) also secreted pro-tumorigenic cytokines to regulate the function of endothelial cells and CAFs. Finally, the patients with low LMAS scores might have better efficacy in immunotherapy.

A LMAS was constructed to guide GC prognosis and therapy. Meanwhile, a novel anti-tumor effect was found in lipid metabolism reprogramming of GC which improved patients' prognosis by regulating the sensitivity of tumor cells to ferroptosis. Moreover, EndMT may have a negative impact on GC prognosis.

Preclinical research has identified the mechanisms via which bacteria influence cancer treatment outcomes. Clinical studies have demonstrated the potential to modify the microbiome in cancer treatment. Herein, we systematically analyze how gut microorganisms interact with chemotherapy and immune checkpoint inhibitors, specifically focusing on how gut bacteria affect the pharmacokinetics and pharmacodynamics of cancer treatment.

This study searched Web of Science, Scopus, and PubMed until August 2023. Studies were screened by their title and abstract using the Rayyan intelligent tool for systematic reviews. Quality assessment of studies was done using the JBI critical appraisal tool.

Alterations in the gut microbiome are associated with gastric cancer and precancerous lesions. These alterations include reduced microbial alpha diversity, increased bacterial overgrowth, and decreased richness and evenness of gastric bacteria. Helicobacter pylori infection is associated with reduced richness and evenness of gastric bacteria, while eradication only partially restores microbial diversity. The gut microbiome also affects the response to cancer treatments, with higher abundances of Lactobacillus associated with better response to anti-PD-1/PD-L1 immunotherapy and more prolonged progression-free survival. Antibiotic-induced gut microbiota dysbiosis can reduce the anti-tumor efficacy of 5-Fluorouracil treatment, while probiotics did not significantly enhance it. A probiotic combination containing Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus can reduce inflammation, enhance immunity, and restore a healthier gut microbial balance in gastric cancer patients after partial gastrectomy.

Probiotics and targeted interventions to modulate the gut microbiome have shown promising results in cancer prevention and treatment efficacy.Systematic review registration: https://osf.io/6vcjp.