Helicobacter pylori and gastric cancer: mechanisms and new perspectives

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 23, 2025

Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as major etiological agent, affecting an estimated 50% of the world's population. There has been rapidly expanding knowledge molecular and pathogenetic mechanisms H. over decades. This review summarizes latest research advances to elucidate underlying infection in gastric carcinogenesis. Our investigation reveals complex network involving STAT3, NF-κB, Hippo, Wnt/β-catenin pathways, which are dysregulated caused by pylori. Furthermore, we highlight role inducing oxidative stress, DNA damage, chronic inflammation, cell apoptosis—key cellular events that pave way for Emerging evidence also suggests effect on tumor microenvironment its possible implications immunotherapy. synthesizes current identifies gaps warrant further investigation. Despite progress our previous development pylori-induced cancer, comprehensive pylori's is crucial advancement prevention treatment strategies. By elucidating these mechanisms, aim provide more in-depth insights study pylori-related cancer.

Language: Английский

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Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Colon adenocarcinoma (COAD) is a malignancy with high mortality rate and complex biological characteristics heterogeneity, which poses challenges for clinical treatment. Anoikis type of programmed cell death that occurs when cells lose their attachment to the extracellular matrix (ECM), it plays crucial role in tumor metastasis. However, specific link between anoikis COAD, as well its mechanisms progression, remains unclear, making potential new direction therapeutic strategy research. We employed transcriptomic data information from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) pinpoint differentially expressed anoikis-related genes (ARGs) COAD. Using Cox proportional hazards models Lasso regression analysis, we developed prognostic signature derived these ARGs. also investigated roles interactions microenvironment by analyzing single-cell RNA sequencing data. Additionally, molecular docking techniques evaluate inhibin subunit beta B (INHBB) targets assess binding affinity candidate drugs. Finally, used gene knockout silence key INHBB explored functions vitro. In our study, expression differences ARGs, successfully classified patients Kaplan-Meier survival analysis demonstrated elevated risk scores experienced poorer prognosis, finding was confirmed both training validation cohorts. immune infiltration revealed notable increase presence within high-risk patients. Molecular identified drug candidates INHBB, including risperidone. Furthermore, vitro experiments showed downregulation COAD lines significantly reduced cellular viability migration capacity. summary, research, based on provides insights into precise classification, prognosis assessment, identification It validates progression establishing foundation future personalized treatment strategies.

Language: Английский

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Integrative analysis of single-cell and bulk RNA sequencing reveals the oncogenic role of ANXA5 in gastric cancer and its association with drug resistance

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 7, 2025

Background Gastric cancer (GC) remains a leading cause of cancer-related mortality, with over one million new cases and 769,000 deaths reported in 2020. Despite advancements chemotherapy, surgery, targeted therapies, delayed diagnosis due to overlooked early symptoms leads poor prognosis. Methods We integrated bulk RNA sequencing single-cell datasets from TCGA, GEO, OMIX001073, employing normalization, batch effect correction, dimensionality reduction methods identify key cell populations associated GC invasion epithelial-mesenchymal transition (EMT), as well analyze the tumor immune microenvironment. Results Our analysis identified MUC5AC+ malignant epithelial cluster significant player EMT. Cluster 1, representing this population, exhibited higher EMT scores compared other clusters. Survival showed that high abundance 0 correlated improved survival rates (P=0.012), whereas 1 was poorer outcomes (P=0.045). A prognostic model highlighted ANXA5 GABARAPL2 two critical genes upregulated tumors. High-risk patients demonstrated increased infiltration worse prognosic. Analysis mutation burden (TMB) indicated low TMB high-risk group had worst Wet-lab validation experiments confirmed oncogenic role ANXA5, showing its facilitation proliferation, invasion, migration while suppressing apoptosis. Conclusion This study offers novel insights into subpopulations cells their roles progression. It provides potential therapeutic targets combat GC, contributing crucial understanding fundamental mechanisms drug resistance gastrointestinal cancers.

Language: Английский

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Analyze the Diversity and Function of Immune Cells in the Tumor Microenvironment From the Perspective of Single‐Cell RNA Sequencing

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(5)

Published: March 1, 2025

Cancer development is closely associated with complex alterations in the tumor microenvironment (TME). Among these, immune cells within TME play a huge role personalized diagnosis and treatment. This review aims to summarize diversity of TME, their impact on patient prognosis treatment response, contributions single-cell RNA sequencing (scRNA-seq) understanding functional heterogeneity. We analyzed recent studies utilizing scRNA-seq investigate cell populations focusing interactions regulatory mechanisms. ScRNA-seq reveals heterogeneity cells, enhances our antibody responses, facilitates construction interaction networks. These insights provide guidance for cancer immunotherapies approaches. Applying analysis offers novel pathway Despite its promise, several challenges remain, highlighting need further advancements fully integrate into clinical applications.

Language: Английский

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Helicobacter pylori infection promotes M1 macrophage polarization and gastric inflammation by activation of NLRP3 inflammasome via TNF/TNFR1 axis

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 6, 2025

Macrophages play a crucial role in chronic gastritis induced by the pathogenic Helicobacter pylori (H. pylori) infection. NLRP3 inflammasome has emerged as an important component of inflammatory processes. However, molecular mechanism which H. infection drives and macrophages activation remains unclear. Human tissues were collected for clinical significance NLRP3. Infection with was performed using vitro vivo models. Bone marrow-derived (BMDMs) from wild-type (WT), Nlrp3-knockout (KO) Tnfr1-KO mice infected pylori. Western blotting, qRT-PCR, immunofluorescence, immunohistochemistry ELISA utilized functional mechanistic studies. Single-cell RNA sequencing (ScRNA-seq) analysis human gastric tissues, followed validation, indicated that primarily expressed myeloid cells significantly increased pylori-positive compared to pylori-negative gastritis. PMSS1 NCTC11637 strains (THP1 cells) insulin-gastrin (INS-GAS) transgenic mouse model. Deletion BMDMs showed marked inhibition pylori-induced M1 macrophage polarization. Furthermore, upon TNFα, or stimulation, partially blocked TNFα/TNFR1 signaling inhibitors. TNFR1 impaired This study revealed inflammasome, regulated TNF/TNFR1 axis, is key regulator

Language: Английский

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Single-cell profiling reveals a reduced epithelial defense system, decreased immune responses and the immune regulatory roles of different fibroblast subpopulations in chronic atrophic gastritis

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 4, 2025

Abstract Purpose To identify key cellular changes and molecular events in atrophic mucosa, we aimed to elucidate the mechanisms driving occurrence of chronic gastritis (CAG). Methods We used single-cell RNA sequencing (scRNA-seq) characterize epithelial state tissue microenvironment associated with CAG. The were identified by comparing differentially expressed genes (DEGs) between two mucosa states. Gene Ontology (GO) pathway enrichment analysis was explore potential functional each cell subtype mucosa. set score conducted compare roles different fibroblast subtypes CAG control groups. Metabolic performed metabolic activity C1Q + macrophages under conditions. NichNet analyze regulatory relationships CCL11 APOE fibroblasts CD8 effector T cells. Transcription factor (TF) determine transcription status T-cell normal Results generated a transcriptomic atlas from 3 biopsy samples paired adjacent tissues. Our revealed that chief cells parietal exhibited loss detoxification ability surface mucous displayed reduced antimicrobial defense lesions. neck lesions showed upregulation related cycle transition, which may lead aberrant DNA replication. Additionally, exhaustion phenotype infiltrated condition. phagocytosis, downregulated expression pattern recognition receptors decreased activity. subpopulation CXCL11 regulated inflammatory response pathogenesis gastritis. APSN found be gastric cancer (GC) development. Conclusions main goal this study comprehensively observed an immune decline mucosal during development CAG, including macrophages, cytotoxicity cells, increased infiltration exhausted Specifically, demonstrated aberrantly express susceptibility external bacterial infection progression. provides new insights into functions alterations

Language: Английский

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Sex-specific effects of gastrointestinal microbiome disruptions on Helicobacter pylori-induced gastric carcinogenesis in INS-GAS mice

Biology of Sex Differences, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 21, 2025

Abstract Background Accumulating evidence indicates that the dysbiosis of gastrointestinal microbiota is associated with development gastric carcinogenesis. However, sex-specific traits and their correlation sexually dimorphic response to cancer remain poorly understood. Methods Male female transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model were randomly administered Brucella Broth or Helicobacter pylori ( H. ). Stomachs evaluated by histopathology. The inflammation was examined immunohistochemical immunofluorescence staining. Gastric mucosal fecal samples collected for analysis using 16S rRNA gene sequencing. Results Following infection, male showed heightened inflammatory infiltration notably greater intestinal metaplasia compared mice. structure different between mice, relative higher diversity in females than males. Notably, we found gender disparities alterations post infection. While enrichment Bifidobacterium Lachnospiraceae observed Escherichia_Shigella Akkermansia more abundant Furthermore, microbial profile distinct estrogen-deficient ovariectomized (OVX) including overgrowth loss Butyricicoccus . Infected OVX developed significantly severe lesions, which normalized through co-housing intact females. Conclusions We have identified novel microbiome-based mechanism provides insight into sexual dimorphism -associated cancer.

Language: Английский

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Helicobacter pylori, microbiota and gastric cancer — principles of microorganism-driven carcinogenesis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Language: Английский

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Identification of Anoikis‐Related Genes in Gastric Cancer: Bioinformatics and Experimental Validation

Cancer Medicine, Journal Year: 2025, Volume and Issue: 14(8)

Published: April 1, 2025

ABSTRACT Introduction Distant metastasis is the main reason for poor prognosis of gastric cancer, and anoikis refers to cell death caused when cells detach from extracellular matrix or adhere in incorrect locations, playing an important role distant cancer. Methods Download TCGA‐STAD dataset gene set, filter out differentially expressed genes. Perform consensus clustering cancer samples, conduct Weighted Gene Correlation Network Analysis (WGCNA), enrichment analysis, immune infiltration analysis expression characteristics each subtype, while also filtering genes with differential between subtypes. Additionally, through COX survival identify related establish a nomogram. Finally, validate CYP1B1 vivo vitro clinical culture, establishment model. Results Three subtypes were identified, exhibiting different characteristics, biological pathways, infiltration. The abundance activated NK cells, memory B M2 macrophages showed significant differences among three We screened four sets five (CYP1B1, EQTN, NRXN2, TBC1D3E, TCEAL5) Through we identified 33 independent prognostic constructed nomogram, calibration curves indicating good consistency. selected experimental validation, experiments demonstrated that highly participates resistance promotes invasion, migration, tumor progression cells. Conclusion patterns based on vary, providing theoretical support future personalized treatment

Language: Английский

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Current research status and hotspots of precancerous lesions of gastric cancer: a bibliometric analysis

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: April 29, 2025

Gastric cancer is the fifth most common worldwide, and its lack of specific symptoms presents a significant challenge for early diagnosis. Therefore, identification detection precancerous lesions gastric (PLGC) are essential prevention. We performed comprehensive bibliometric analysis to explore research trends emerging topics in this field, aiming deepen our understanding PLGC. This study utilizes approach with network progress PLGC research. The findings aim provide foundation guidance further in-depth investigations into used VOSviewer CiteSpace software collect relevant literature on from Web Science Core Collection, covering period 2005 2024. Data visualization was number publications, countries, institutions, journals, authors, keywords, citation counts these articles. A total 1,141 articles were included analysis. results showed year-on-year increase publications country, institution, author, journal highest publication output field China, Peking University, Wei-Cheng You, World Journal Gastroenterology, respectively. frequently occurring keywords "Helicobacter pylori," "intestinal metaplasia," "risk," "infection," "atrophic gastritis." Additionally, "chronic atrophic gastritis" "inflammation" have emerged as hot future highlights research, valuable studies. Our indicate that mechanistic studies clinical diagnosis will be key areas focus upcoming

Language: Английский

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