NOTCH Target Gene HES5 Distinct Anti-Tumorigenic Roles in Gastric Carcinoma

Abstract I. Background:Gastric cancer (GC) is ranked the third greatest cause of mortality globally and the second common cancer in Iran. To date, many pathways including HES family have been found to be linked to cellular proliferation, differentiation and cancer. HES5, a transcription factor that binds to DNA, is known as a downstream protein in Notch pathway. Therefore, we aimed to investigate the association between HES5 expression and GC.II. Methods and Results:In this study,75 gastric cancer patients were included. After RNA extraction and cDNA synthesis, the expression rate of HES5 was evaluated by quantitative Real-time PCR. Also, presence of H. Pylori infection was verified using specific primers set for H. pylori, and PCR on extracted DNA. The results showed a remarkable decrease in HES level in malignant tissues when compared to the neighboring non-cancerous tissues (Normal) (P< 0.0001). Moreover, an inverse relation between down regulation of HES 5 gene and H.Pylori infection was identified. In conclusionIII. Conclusions: These findings emphasize that HES5 may notably suppress the tumor development.

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Western-Type Helicobacter pylori CagA are the Most Frequent Type in Mongolian Patients

Cancers ◽

10.3390/cancers11050725 ◽

2019 ◽

Vol 11 (5) ◽

pp. 725 ◽

Cited By ~ 2

Author(s):

Tegshee Tserentogtokh ◽

Boldbaatar Gantuya ◽

Phawinee Subsomwong ◽

Khasag Oyuntsetseg ◽

Dashdorj Bolor ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Cancer Patients ◽

East Asian ◽

Virulent Strains ◽

Virulent Type ◽

High Incidence ◽

Caga Status ◽

H Pylori ◽

Gastric Cancer Patients

Helicobacter pylori infection possessing East-Asian-type CagA is associated with carcinogenesis. Mongolia has the highest mortality rate from gastric cancer. Therefore, we evaluated the CagA status in the Mongolian population. High risk and gastric cancer patients were determined using endoscopy and histological examination. H. pylori strains were isolated from different locations in Mongolia. The CagA subtypes (East-Asian-type or Western-type, based on sequencing of Glu-Pro-Ile-Tyr-Ala (EPIYA) segments) and vacA genotypes (s and m regions) were determined using PCR-based sequencing and PCR, respectively. In total, 368 patients were examined (341 gastritis, 10 peptic ulcer, and 17 gastric cancer). Sixty-two (16.8%) strains were cagA-negative and 306 (83.1%) were cagA-positive (293 Western-type, 12 East-Asian-type, and one hybrid type). All cagA-negative strains were isolated from gastritis patients. In the gastritis group, 78.6% (268/341) had Western-type CagA, 2.9% (10/341) had East-Asian-type, and 18.2% (61/341) were cagA-negative. However, all H. pylori from gastric cancer patients possessed Western-type CagA. Histological analyses showed that East-Asian-type CagA was the most virulent strains, followed by Western-type and cagA-negative strains. This finding agreed with the current consensus. CagA-positive strains were the most virulent type. However, the fact that different CagA types can explain the high incidence of gastric cancer might be inapplicable in Mongolia.

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Once-daily, low-cost, highly effective H. pylori (HP)treatment to family members of gastric cancer patients

The American Journal of Gastroenterology ◽

10.1016/s0002-9270(02)04649-x ◽

2002 ◽

Vol 97 (9) ◽

pp. S59

Author(s):

L COELHO

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Low Cost ◽

Family Members ◽

Once Daily ◽

Highly Effective ◽

H Pylori ◽

Gastric Cancer Patients

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Antioxidant-Rich Diet, GSTP1 rs1871042 Polymorphism, and Gastric Cancer Risk in a Hospital-Based Case-Control Study

Frontiers in Oncology ◽

10.3389/fonc.2020.596355 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jimi Kim ◽

Hyejin Kim ◽

Jeonghee Lee ◽

Il Ju Choi ◽

Young-Il Kim ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Risk ◽

Genetic Variants ◽

Total Phenolics ◽

Nucleotide Polymorphisms ◽

Gastric Cancer Risk ◽

Glutathione S Transferase ◽

Dietary Antioxidant ◽

H Pylori ◽

Gastric Cancer Patients

BackgroundChronic gastritis along with Helicobacter pylori (H. pylori) infection has been implicated in inflammatory response-related genes linked to the causation of gastric cancer. Glutathione S-transferase Pi (GSTP1) plays a role in regulating oxidative stress and detoxification against carcinogenesis. In this study, we aimed to determine whether an antioxidant-rich diet is associated with gastric cancer risk and identify how this association could be altered by GSTP1 genetic variants.MethodsThis study included 1,245 participants (415 cases and 830 controls) matched for age and sex. The dietary antioxidant capacity was estimated based on the oxygen radical absorbance capacity (ORAC) incorporated with a semiquantitative food frequency questionnaire. Five single nucleotide polymorphisms (SNPs) of GSTP1 (rs1695, rs749174, rs1871042, rs4891, and rs947895) were selected among the exome array genotype data.ResultsHigh dietary ORAC was inversely associated with gastric cancer (hydrophilic ORAC OR T3vs. T1, 95% CI = 0.57, 0.39–0.82, P = 0.004; lipophilic ORAC = 0.66, 0.45–0.95, P = 0.021; total phenolics = 0.57, 0.39–0.83, P = 0.005). The polymorphism rs1871042 increased the risk of gastric cancer (OR, 95% CI = 1.55, 1.10–2.16, P = 0.01, CT+TT vs. CC). A remarkably reduced risk of gastric cancer was observed among those who had a high dietary ORAC according to rs1871042 polymorphism (hydrophilic ORAC OR T3vs. T1, 95% CI = 0.36, 0.17–0.78, P for trend = 0.013; lipophilic ORAC = 0.58, 0.37–0.93, P for trend = 0.021; total phenolics = 0.38, 0.17–0.83, P for trend = 0.019).ConclusionsOur findings indicate that dietary ORAC intake may be inversely associated with the risk of gastric cancer altered by genetic variants of GSTP1, providing new intervention strategies for gastric cancer patients.

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SNP-SNP interactions of three new pri-miRNAs with the target gene PGC and multidimensional analysis of H. pylori in the gastric cancer/atrophic gastritis risk in a Chinese population

Oncotarget ◽

10.18632/oncotarget.8057 ◽

2016 ◽

Vol 7 (17) ◽

pp. 23700-23714 ◽

Cited By ~ 11

Author(s):

Qian Xu ◽

Ye-feng Wu ◽

Ying Li ◽

Cai-yun He ◽

Li-ping Sun ◽

...

Keyword(s):

Gastric Cancer ◽

Atrophic Gastritis ◽

Chinese Population ◽

Target Gene ◽

Multidimensional Analysis ◽

H Pylori

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Analysis of the potential correlation between gastric cancer and gastrointestinal microbiota via in-silico data mining

10.21203/rs.2.17921/v1 ◽

2019 ◽

Author(s):

Xuelu Ding ◽

Yukun Zhu ◽

Zhaoyuan She ◽

Xuewen Liu ◽

Cancan Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Data Mining ◽

Gastrointestinal Microbiota ◽

Gastrointestinal Microbiome ◽

Helicobactor Pylori ◽

Significant Difference ◽

H Pylori ◽

Gastric Cancer Patients ◽

Insight Into ◽

Gwas Catalog

Abstract Background: Emerging evidence shows the gastrointestinal microbiome might play an important role in the carcinogenesis of gastric cancer. While Helicobactor pylori has been reported to be a specific risk factor of gastric cancer, it is still controversial whether significant difference of non- H. pylori microbiota exists between gastric cancer patients and healthy control.Results: In this study, we employed multiple bioinformatic databases to excavate the potential correlation between gastrointestinal microbiome and gastric cancer. The databases involved in this investigation include HMDB, STITCH, OMIM, GWAS Catalog, WebGestalt, Toppgene, GeneMANIA. In addition, the network diagrams were built by use of Cytoscape software. Notably, our results showed that 33 common genes participate in both gastrointestinal microbiome and gastric cancer. The further analysis of these common genes suggested that there was a wide array of interactions and pathways in which the correlation between gastrointestinal microbiome and gastric cancer is involved.Conclusions: Our present study gives a bioinformatic insight into possible pathways in which the gastrointestinal microbiome play roles in gastric cancer. Future efforts are necessary to be paid to elicit the exact mechanisms as well as potential therapeutic targets of gastric cancer.

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Higher Frequency of CagA EPIYA-C Phosphorylation Sites in H. pylori Strains From Relatives of Gastric Cancer Patients

Gastroenterology ◽

10.1016/s0016-5085(11)61929-x ◽

2011 ◽

Vol 140 (5) ◽

pp. S-469

Author(s):

Gifone A. Rocha ◽

Dulciene M. Queiroz ◽

Andreia Maria C. Rocha ◽

Sérgio A. Batista ◽

Cícero M. Silva ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Phosphorylation Sites ◽

H Pylori ◽

Gastric Cancer Patients

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Functional Analysis of the cag Pathogenicity Island in Helicobacter pylori Isolates from Patients with Gastritis, Peptic Ulcer, and Gastric Cancer

Infection and Immunity ◽

10.1128/iai.72.2.1043-1056.2004 ◽

2004 ◽

Vol 72 (2) ◽

pp. 1043-1056 ◽

Cited By ~ 87

Author(s):

Steffen Backert ◽

Tobias Schwarz ◽

Stephan Miehlke ◽

Christian Kirsch ◽

Christian Sommer ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Peptic Ulcer ◽

Pathogenicity Island ◽

Epidemiological Studies ◽

Disease Development ◽

Gastric Diseases ◽

H Pylori ◽

Gastric Cancer Patients

ABSTRACT Helicobacter pylori is the causative agent of a variety of gastric diseases, but the clinical relevance of bacterial virulence factors is still controversial. Virulent strains carrying the cag pathogenicity island (cagPAI) are thought to be key players in disease development. Here, we have compared cagPAI-dependent in vitro responses in H. pylori isolates obtained from 75 patients with gastritis, peptic ulcer, and gastric cancer (n = 25 in each group). AGS gastric epithelial cells were infected with each strain and assayed for (i) CagA expression, (ii) translocation and tyrosine phosphorylation of CagA, (iii) c-Src inactivation, (iv) cortactin dephosphorylation, (v) induction of actin cytoskeletal rearrangements associated with cell elongation, (vi) induction of cellular motility, and (vii) secretion of interleukin-8. Interestingly, we found high but similar prevalences of all of these cagPAI-dependent host cell responses (ranging from 56 to 80%) among the various groups of patients. This study revealed CagA proteins with unique features, CagA subspecies of various sizes, and new functional properties for the phenotypic outcomes. We further showed that induction of AGS cell motility and elongation are two independent processes. Our data corroborate epidemiological studies, which indicate a significant association of cagPAI presence and functionality with histopathological findings in gastritis, peptic ulcer, and gastric cancer patients, thus emphasizing the importance of the cagPAI for the pathogenicity of H. pylori. Nevertheless, we found no significant association of the specific H. pylori-induced responses with any particular patient group. This may indicate that the determination of disease development is highly complex and involves multiple bacterial and/or host factors.

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Precancerous Gastric Lesions with Helicobacter pylori vacA+/babA2+/oipA+ Genotype Increase the Risk of Gastric Cancer

BioMed Research International ◽

10.1155/2020/7243029 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Theeraya Simawaranon Bartpho ◽

Wareeporn Wattanawongdon ◽

Taweesak Tongtawee ◽

Chatchanok Paoin ◽

Kokiet Kangwantas ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Clinical Outcomes ◽

Chronic Gastritis ◽

Virulence Genes ◽

Gastric Lesions ◽

Precancerous Gastric Lesions ◽

Increased Risk ◽

H Pylori ◽

Gastric Cancer Patients

Objective. The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods. Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori infection and virulence genes (cagA, vacA, iceA2, babA2, and oipA) were determined using real-time PCR. The association between H. pylori genotypes and clinical outcomes were evaluated using multivariate regression model analysis. The overall survival of gastric cancer patients was compared between genotype combinations. Results. H. pylori was positive in 166 patients with chronic gastritis, precancerous gastric lesions, and gastric cancer. The genes vacA, babA2, and oipA were most prevalent in chronic gastritis (73%), precancerous gastric lesions (62%), and gastric cancer (91%), respectively. The vacA, babA2, and oipA genes were associated with increased risk of gastric cancer (OR = 1.23; 95% CI = 1.13–3.32; P=0.033, OR = 2.64; 95% CI = 1.44–4.82, P=0.024, and OR = 2.79; 95% CI = 1.58–5.41; P=0.031, respectively). Interestingly, H. pylori vacA+/babA2+/oipA+ genotype infection was associated with increased risk of gastric cancer (OR = 3.85, 95% CI = 1.67–5.77, P=0.014). Conclusion. In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.

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