scholarly journals Analysis of the prognostic biomarkers associated with cancer stem cell characteristics and immune infiltration of Helicobacter pylori-induced gastric cancer

2021 ◽  
Author(s):  
Qili Chen ◽  
Xuemei Lv ◽  
Shuqi Zhou ◽  
Yuanyuan Yan ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
T Cells ◽  
Helicobacter Pylori ◽  
Cytokine Signaling ◽  
Major Function ◽  
Immune Infiltration ◽  
Key Genes ◽  
H Pylori ◽  
High Level

Abstract BackgroundChina is a country with a high incidence of gastric cancer, accounting for about half of the new cases in the world every year. The development of Gastric cancer (GC) is closely related to Helicobacter pylori (H. pylori) infection. Cancer stem cells (CSCs) play important roles in the survival, proliferation, metastasis and recurrence of tumors. However, the mechanism of CSCs and H. pylori-induced GC remains unclear.At the same time, the effect of tumor microenvironment on tumor stem cells and GC with H. pylori infection is also worth exploring. On the basis of the existing research on GC, it is still of great significance to further understand and explore the pathogenesis of GC through bioinformatics analysis.ResultsThere was higher mRNA expression-based stemness index (mRNAsi) in H. pylori (+) GC tumor tissue than in normal tissue. The clinical features of stage T and N were highly correlated with mRNAsi. The purple module was the most significant modules related to the mRNAsi by WGCNA and its key genes played played a major function related to tumor immunity, mainly involved in regulating the Jak-STAT signal pathway, Th17 cell differentiation pathway, and so on. These key genes were correlated with the high level of immune infiltration of CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in GC via Tumor Immune Estimation Resource (TIMER). 28 genes were found to be closely related to the characteristics of gastric CSCs (GCSCs) associated with H. pylori infection. 13 genes were associated with lymph node metastasis in GC, which may lead to poor prognosis in patients.ConclusionThe characteristics of GCSCs were related to the interleukins signaling, cytokine signaling, Jak-STAT signaling pathway, which provides a new idea for screening therapeutic targets to inhibit the characteristics of GCSCs and a basis for the eradication of H. pylori and the prevention of GC.

Increased Production of Matrix Metalloproteinases in Helicobacter pylori Infection that Stimulates Gastric Cancer Stem Cells

2020 ◽  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Helicobacter Pylori ◽  
Cancer Stem Cells ◽  
Histopathological Examination ◽  
Physiological Saline ◽  
Rrna Gene ◽  
Peptic Ulcers ◽  
Gastric Cancer Stem Cells ◽  
H Pylori

Background and aim: Helicobacter pylori (H. pylori) is an incriminated pathogen causing diseases in both animals and humans and considered a zoonotic pathogen. H. pylori infection is considered a cause of gastric cancer, which rests a significant health care challenge. This study analyzes the expression pattern of matrix metalloprotein 2 (MMP-2) in patients with Helicobacter pylori-associated gastritis and the effect of H. pylori on gastric cancer stem cells, as well as study the role of helicon bacteriosis in dog in transmission of H. pylori infection to human. Materials and methods: Fifty-five of each sample (gastric biopsy, blood and stool) were collected from patients suffering from dyspepsia, chronic vomiting and perforated peptic ulcers and also from apparent healthy dogs. The investigation detected H. pylori by serological and histopathological examination. Biopsies were stored in physiological saline for identification of H. pylori by conventional time PCR. MMP-2 and Gastric cancer stem cells were then identified by immunohistochemistry. Results: Serological identification for H. pylori Antigen and Antibodies revealed (63% human, 50% dogs) and (87% human, 90% dogs) respectively were positive. Genotyping of H. pylori based on 16S rRNA gene showed 54.5% of human and 35% of dogs were positive. Immunohistochemistry revealed strong expression of CD44 in H. pylori- associated gastric cancer cases, MMP-2 expression was observed in all neoplastic lesions associated with H. pylori infection. Conclusion: H. pylori infection affects gastric mucosa and induces changes in gastric stem cells altering their differentiation and increased expression of MMP’s and CD44with a resultant potentiation of oncogenic alteration. In addition the up-regulation of both markers could be an instrumental to interpret the origination of gastric cancer.

Bone Marrow-Derived Mesenchymal Stem Cells Favor the Immunosuppressive T Cells Skewing in a Helicobacter Pylori Model of Gastric Cancer

2013 ◽  
Vol 22 (21) ◽  
pp. 2836-2848 ◽  
Author(s):  
Rong Lin ◽  
Huan Ma ◽  
Zhen Ding ◽  
Weina Shi ◽  
Wei Qian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
T Cells ◽  
Helicobacter Pylori ◽  
Mesenchymal Stem Cells

scholarly journals Rejuvenation of Helicobacter pylori–Associated Atrophic Gastritis Through Concerted Actions of Placenta-Derived Mesenchymal Stem Cells Prevented Gastric Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jong Min Park ◽  
Young Min Han ◽  
Ki Baik Hahm
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Helicobacter Pylori ◽  
Mesenchymal Stem Cells ◽  
Atrophic Gastritis ◽  
Conditioned Medium ◽  
Gastric Atrophy ◽  
Control Group ◽  
Therapeutic Effects ◽  
H Pylori

Chronic Helicobacter pylori infection causes gastric cancer via the progression of precancerous chronic atrophic gastritis (CAG). Therefore, repairing gastric atrophy could be a useful strategy in preventing H. pylori–associated gastric carcinogenesis. Although eradication of the bacterial pathogen offers one solution to this association, this study was designed to evaluate an alternative approach using mesenchymal stem cells to treat CAG and prevent carcinogenesis. Here, we used human placenta-derived mesenchymal stem cells (PD-MSCs) and their conditioned medium (CM) to treat H. pylori–associated CAG in a mice/cell model to explore their therapeutic effects and elucidate their molecular mechanisms. We compared the changes in the fecal microbiomes in response to PD-MSC treatments, and chronic H. pylori–infected mice were given ten treatments with PD-MSCs before being sacrificed for end point assays at around 36 weeks of age. These animals presented with significant reductions in the mean body weights of the control group, which were eradicated following PD-MSC treatment (p < 0.01). Significant changes in various pathological parameters including inflammation, gastric atrophy, erosions/ulcers, and dysplastic changes were noted in the control group (p < 0.01), but these were all significantly reduced in the PD-MSC/CM-treated groups. Lgr5+, Ki-67, H+/K+-ATPase, and Musashi-1 expressions were all significantly increased in the treated animals, while inflammatory mediators, MMP, and apoptotic executors were significantly decreased in the PD-MSC group compared to the control group (p < 0.001). Our model showed that H. pylori–initiated, high-salt diet–promoted gastric atrophic gastritis resulted in significant changes in the fecal microbiome at the phylum/genus level and that PD-MSC/CM interventions facilitated a return to more normal microbial communities. In conclusion, administration of PD-MSCs or their conditioned medium may present a novel rejuvenating agent in preventing the progression of H. pylori–associated premalignant lesions.

scholarly journals Helicobacter pylori Infection-Induced Hepatoma-Derived Growth Factor Regulates the Differentiation of Human Mesenchymal Stem Cells to Myofibroblast-Like Cells

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 479 ◽  
Author(s):  
Chung-Jung Liu ◽  
Yao-Kuang Wang ◽  
Fu-Chen Kuo ◽  
Wen-Hung Hsu ◽  
Fang-Jung Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Stem Cells ◽  
Helicobacter Pylori ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Tumor Cell ◽  
Critical Role ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
H Pylori

Hepatoma-derived growth factor (HDGF) plays a critical role in tumor cell proliferation, anti-apoptosis, VEGF expression, lymph node metastasis and poor prognosis in human gastric cancer. Gastric cancer, as one of the most prevalent cancers worldwide, is the second leading cause of cancer-related mortality in the world for the prognosis of gastric cancer is generally poor, especially in patients with advanced stage. Helicobacter pylori (H. pylori) infection causes the chronic inflammation of stomach as well as the development of gastric cancer, with a three to six-fold increased risk of gastric cancer. Carcinoma-associated fibroblasts (CAFs) are myofibroblasts in tumor microenvironment, which possess various abilities to promote the progression of cancer by stimulating neoangiogenesis, proliferation, migration, invasion and therapy resistance of tumor cell. Mesenchymal stem cells (MSCs) are reported to promote tumor malignance through differentiation of MSCs toward CAFs. In the present study, we demonstrated that H. pylori infection promotes HDGF expression in human gastric cancer cells. HBMMSCs treated with HDGF assume properties of CAF-like myofibroblastic phenotypes, including expression of myofibroblast markers (α-smooth muscle actin (α-SMA), procollagen α1, tropomyoson I, desmin, fibroblast activation protein (FAP)), and fibroblast markers (prolyl-4-hydroxylase A1 (PHA1) and fibroblast specific protein-1 (FSP-1)/S100A4). HDGF recruits HBMMSCs, and then HBMMSCs further contributes to cell survival and invasive motility in human gastric cancer cells. Treatment of HDGF neutralizing antibody (HDGF-NAb) and serum significantly inhibit HDGF-regulated differentiation and recruitment of HBMMSCs. These findings suggest that HDGF might play a critical role in gastric cancer progress through stimulation of HBMMSCs differentiation to myofibroblast-like cells.

scholarly journals The correlation between lncRNAs and Helicobacter pylori in gastric cancer

2019 ◽  
Vol 77 (9) ◽  
Author(s):  
Narges Dastmalchi ◽  
Seyed Mahdi Banan Khojasteh ◽  
Mirsaed Miri Nargesi ◽  
Reza Safaralizadeh
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Gastrointestinal Diseases ◽  
Mechanisms Of Action ◽  
Molecular Pathways ◽  
Gastric Diseases ◽  
Non Coding Rnas ◽  
H Pylori ◽  
The Relationship

ABSTRACT Helicobacter pylori infection performs a key role in gastric tumorigenesis. Long non-coding RNAs (lncRNAs) have demonstrated a great potential to be regarded as effective malignancy biomarkers for various gastrointestinal diseases including gastric cancer (GC). The present review highlights the relationship between lncRNAs and H. pylori in GC. Several studies have examined not only the involvement of lncRNAs in H. pylori-associated GC progression but also their molecular mechanisms of action. Among the pertinent studies, some have addressed the effects of H. pylori infection on modulatory networks of lncRNAs, while others have evaluated the effects of changes in the expression level of lncRNAs in H. pylori-associated gastric diseases, especially GC. The relationship between lncRNAs and H. pylori was found to be modulated by various molecular pathways.

scholarly journals Helicobacter pylori Outer Membrane Vesicles and Extracellular Vesicles from Helicobacter pylori-Infected Cells in Gastric Disease Development

2021 ◽  
Vol 22 (9) ◽  
pp. 4823
Author(s):  
María Fernanda González ◽  
Paula Díaz ◽  
Alejandra Sandoval-Bórquez ◽  
Daniela Herrera ◽  
Andrew F. G. Quest
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Outer Membrane ◽  
Extracellular Vesicles ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Host Cells ◽  
Gastric Epithelium ◽  
Infected Cells ◽  
H Pylori

Extracellular vesicles (EVs) are cell-derived vesicles important in intercellular communication that play an essential role in host-pathogen interactions, spreading pathogen-derived as well as host-derived molecules during infection. Pathogens can induce changes in the composition of EVs derived from the infected cells and use them to manipulate their microenvironment and, for instance, modulate innate and adaptive inflammatory immune responses, both in a stimulatory or suppressive manner. Gastric cancer is one of the leading causes of cancer-related deaths worldwide and infection with Helicobacter pylori (H. pylori) is considered the main risk factor for developing this disease, which is characterized by a strong inflammatory component. EVs released by host cells infected with H. pylori contribute significantly to inflammation, and in doing so promote the development of disease. Additionally, H. pylori liberates vesicles, called outer membrane vesicles (H. pylori-OMVs), which contribute to atrophia and cell transformation in the gastric epithelium. In this review, the participation of both EVs from cells infected with H. pylori and H. pylori-OMVs associated with the development of gastric cancer will be discussed. By deciphering which functions of these external vesicles during H. pylori infection benefit the host or the pathogen, novel treatment strategies may become available to prevent disease.

scholarly journals Role of TNF-α-Inducing Protein Secreted by Helicobacter pylori as a Tumor Promoter in Gastric Cancer and Emerging Preventive Strategies

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 181
Author(s):  
Masami Suganuma ◽  
Tatsuro Watanabe ◽  
Eisaburo Sueoka ◽  
In Kyoung Lim ◽  
Hirota Fujiki
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cell Surface Receptor ◽  
Tumor Promoter ◽  
Cancer Development ◽  
Human Gastric Cancer ◽  
Tnf Α ◽  
Surface Receptor ◽  
H Pylori ◽  
Factor Α

The tumor necrosis factor-α (TNF-α)-inducing protein (tipα) gene family, comprising Helicobacter pylori membrane protein 1 (hp-mp1) and tipα, has been identified as a tumor promoter, contributing to H. pylori carcinogenicity. Tipα is a unique H. pylori protein with no similarity to other pathogenicity factors, CagA, VacA, and urease. American H. pylori strains cause human gastric cancer, whereas African strains cause gastritis. The presence of Tipα in American and Euro-Asian strains suggests its involvement in human gastric cancer development. Tipα secreted from H. pylori stimulates gastric cancer development by inducing TNF-α, an endogenous tumor promoter, through its interaction with nucleolin, a Tipα receptor. This review covers the following topics: tumor-promoting activity of the Tipα family members HP-MP1 and Tipα, the mechanism underlying this activity of Tipα via binding to the cell-surface receptor, nucleolin, the crystal structure of rdel-Tipα and N-terminal truncated rTipα, inhibition of Tipα-associated gastric carcinogenesis by tumor suppressor B-cell translocation gene 2 (BTG2/TIS21), and new strategies to prevent and treat gastric cancer. Thus, Tipα contributes to the carcinogenicity of H. pylori by a mechanism that differs from those of CagA and VacA.

scholarly journals Diversity of 3′ variable region of cagA gene in Helicobacter pylori strains isolated from Chinese population

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Zhijing Xue ◽  
Yuanhai You ◽  
Lihua He ◽  
Yanan Gong ◽  
Lu Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Amino Acid ◽  
Chinese Population ◽  
Statistical Difference ◽  
Variable Region ◽  
Repeat Region ◽  
Geographical Regions ◽  
H Pylori ◽  
Epiya Motifs

Abstract Background The cytotoxin-associated gene A (cagA) is one of the most important virulence factors of Helicobacter pylori (H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal of CagA protein. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity of cagA 3′ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region of H. pylori, and their association with gastroduodenal diseases. Methods A total of 515 H. pylori strains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and the cagA 3′ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software. Results A total of 503 (97.7%) H. pylori strains were cagA-positive and 1,587 EPIYA motifs were identified, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B′, B″ and D′) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which included AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographical regions (P = 0.006). There were seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acids 893 and 894 had a statistical difference with gastric cancer (P = 0.004). Conclusions In this study, 503 CagA sequences were studied and analyzed in depth. In Chinese population, most H. pylori strains were of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residues 893 and 894 flanking the EPIYA motifs had a statistically significant association with gastric cancer.

scholarly journals Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 27
Author(s):  
Jacek Baj ◽  
Alicja Forma ◽  
Monika Sitarz ◽  
Piero Portincasa ◽  
Gabriella Garruti ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Virulence Factors ◽  
Premalignant Lesions ◽  
Bacterial Pathogenicity ◽  
Current State ◽  
Genetic And Environmental Factors ◽  
H Pylori ◽  
Stimulation Of

Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.

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