scholarly journals Discovery and Validation of Novel Methylation Markers in Helicobacter pylori-Associated Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Huan Wang ◽  
Nian-Shuang Li ◽  
Cong He ◽  
Chuan Xie ◽  
Yin Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Helicobacter Pylori ◽  
Gene Expression Data ◽  
Functional Enrichment ◽  
Expression Data ◽  
H Pylori

Previous studies have shown that abnormal methylation is an early key event in the pathogenesis of most human cancers, contributing to the development of tumors. However, little attention has been given to the potential of DNA methylation patterns as markers for Helicobacter pylori- (H. pylori-) associated gastric cancer (GC). In this study, an integrated analysis of DNA methylation and gene expression was conducted to identify some potential key epigenetic markers in H. pylori-associated GC. DNA methylation data of 28 H. pylori-positive and 168 H. pylori-negative GC samples were compared and analyzed. We also analyzed the gene expression data of 18 H. pylori-positive and 145 H. pylori-negative GC cases. Finally, the results were verified by in vitro and in vivo experiments. A total of 5609 differentially methylated regions associated with 2454 differentially methylated genes were identified. A total of 228 differentially expressed genes were identified from the gene expression data of H. pylori-positive and H. pylori-negative GC cases. The screened genes were analyzed for functional enrichment. Subsequently, we obtained 28 genes regulated by methylation through a Venn diagram, and we identified five genes (GSTO2, HUS1, INTS1, TMEM184A, and TMEM190) downregulated by hypermethylation. HUS1, GSTO2, and TMEM190 were expressed at lower levels in GC than in adjacent samples ( P < 0.05 ). Moreover, H. pylori infection decreased HUS1, GSTO2, and TMEM190 expression in vitro and in vivo. Our study identified HUS1, GSTO2, and TMEM190 as novel methylation markers for H. pylori-associated GC.

scholarly journals Pan-genomic analyses identify key Helicobacter pylori pathogenic loci modified by carcinogenic host microenvironments

Gut ◽  
2017 ◽  
Vol 67 (10) ◽  
pp. 1793-1804 ◽  
Author(s):  
Jennifer M Noto ◽  
Abha Chopra ◽  
John T Loh ◽  
Judith Romero-Gallo ◽  
M Blanca Piazuelo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Genetic Variation ◽  
Prolonged Exposure ◽  
Dietary Factors ◽  
High Salt ◽  
Premalignant Lesions ◽  
H Pylori

ObjectiveHelicobacter pylori is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of H. pylori to in vivo carcinogenic microenvironments results in genetic modification important for disease.DesignWhole genome sequencing of genetically related H. pylori strains that differ in virulence and targeted H. pylori sequencing following prolonged exposure of bacteria to in vitro carcinogenic conditions were performed.ResultsA total of 180 unique single nucleotide polymorphisms (SNPs) were identified among the collective genomes when compared with a reference H. pylori genome. Importantly, common SNPs were identified in isolates harvested from iron-depleted and high salt carcinogenic microenvironments, including an SNP within fur (FurR88H). To investigate the direct role of low iron and/or high salt, H. pylori was continuously cultured in vitro under low iron or high salt conditions to assess fur genetic variation. Exposure to low iron or high salt selected for the FurR88H variant after only 5 days. To extend these results, fur was sequenced in 339 clinical H. pylori strains. Among the isolates examined, 17% (40/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6/107) of strains from patients with non-atrophic gastritis alone (p=0.0034).ConclusionThese results indicate that specific genetic variation arises within H. pylori strains during in vivo adaptation to conditions conducive for gastric carcinogenesis.

scholarly journals A Novel Biomarker Identification Approach for Gastric Cancer Using Gene Expression and DNA Methylation Dataset

2021 ◽  
Vol 12 ◽  
Author(s):  
Ge Zhang ◽  
Zijing Xue ◽  
Chaokun Yan ◽  
Jianlin Wang ◽  
Huimin Luo
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Feature Selection ◽  
Gene Expression Data ◽  
Complex Disease ◽  
Biological Data ◽  
Computational Method ◽  
Superior Performance ◽  
Expression Data

As one type of complex disease, gastric cancer has high mortality rate, and there are few effective treatments for patients in advanced stage. With the development of biological technology, a large amount of multiple-omics data of gastric cancer are generated, which enables computational method to discover potential biomarkers of gastric cancer. That will be very important to detect gastric cancer at earlier stages and thus assist in providing timely treatment. However, most of biological data have the characteristics of high dimension and low sample size. It is hard to process directly without feature selection. Besides, only using some omic data, such as gene expression data, provides limited evidence to investigate gastric cancer associated biomarkers. In this research, gene expression data and DNA methylation data are integrated to analyze gastric cancer, and a feature selection approach is proposed to identify the possible biomarkers of gastric cancer. After the original data are pre-processed, the mutual information (MI) is applied to select some top genes. Then, fold change (FC) and T-test are adopted to identify differentially expressed genes (DEG). In particular, false discover rate (FDR) is introduced to revise p_value to further screen genes. For chosen genes, a deep neural network (DNN) model is utilized as the classifier to measure the quality of classification. The experimental results show that the approach can achieve superior performance in terms of accuracy and other metrics. Biological analysis for chosen genes further validates the effectiveness of the approach.

scholarly journals In VivoExpression of Helicobacter pylori Virulence Genes in Patients with Gastritis, Ulcer, and Gastric Cancer

2011 ◽  
Vol 80 (2) ◽  
pp. 594-601 ◽  
Author(s):  
Francisco Avilés-Jiménez ◽  
Adriana Reyes-Leon ◽  
Erik Nieto-Patlán ◽  
Lori M. Hansen ◽  
Juan Burgueño ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Environmental Conditions ◽  
Virulence Genes ◽  
Content Type ◽  
Ulcer Disease ◽  
Type Iv ◽  
H Pylori

ABSTRACTThe best-studiedHelicobacter pylorivirulence factor associated with development of peptic ulcer disease or gastric cancer (GC) rather than asymptomatic nonatrophic gastritis (NAG) is thecagpathogenicity island (cagPAI), which encodes a type IV secretion system (T4SS) that injects the CagA oncoprotein into host epithelial cells. Here we used real-time reverse transcription-PCR (RT-PCR) to measure thein vivoexpression of genes on thecagPAI and of other virulence genes in patients with NAG, duodenal ulcer (DU), or GC.In vivoexpression ofH. pylorivirulence genes was greater overall in gastric biopsy specimens of patients with GC than in those of patients with NAG or DU. However, sincein vitroexpression ofcagAwas not greater inH. pyloristrains from patients with GC than in those from patients with NAG or DU, increased expression in GCin vivois likely a result of environmental conditions in the gastric mucosa, though it may in turn cause more severe pathology. Increased expression of virulence genes in GC may represent a stress response to elevated pH or other environmental conditions in the stomach of patients with GC, which may be less hospitable toH. pyloricolonization than the acidic environment in patients with NAG or DU.

scholarly journals Assessing Chemical-Induced Liver Injury In Vivo From In Vitro Gene Expression Data in the Rat: The Case of Thioacetamide Toxicity

2019 ◽  
Vol 10 ◽  
Author(s):  
Patric Schyman ◽  
Richard L. Printz ◽  
Shanea K. Estes ◽  
Tracy P. O’Brien ◽  
Masakazu Shiota ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Injury ◽  
Gene Expression Data ◽  
Expression Data

scholarly journals Clinical Drug Response Prediction by Using a Lq Penalized Network-Constrained Logistic Regression Method

2018 ◽  
Vol 51 (5) ◽  
pp. 2073-2084 ◽  
Author(s):  
Hai-Hui Huang ◽  
Jing-Guo Dai ◽  
Yong Liang
Keyword(s):  
Gene Expression ◽  
Logistic Regression ◽  
Personalized Medicine ◽  
Gene Expression Data ◽  
Drug Response ◽  
Prediction Models ◽  
Response Prediction ◽  
Expression Data

Background/Aims: One of the most important impacts of personalized medicine is the connection between patients’ genotypes and their drug responses. Despite a series of studies exploring this relationship, the predictive ability of such analyses still needs to be strengthened. Methods: Here we present the Lq penalized network-constrained logistic regression (Lq-NLR) method to meet this need, in which the predictors are integrated into the gene expression data and biological network knowledge and are combined with a more aggressive penalty function. Response prediction models for two cancer targeting drugs (erlotinib and sorafenib) were developed from gene expression data and IC50 values from a large panel of cancer cell lines by utilizing the proposed approach. Then the drug responders were tested with the baseline tumor gene expression data, yielding an in vivo drug sensitivity prediction. Results: These results demonstrated the high effectiveness of this approach. One of the best results achieved by our method was a correlation of 0.841 between the cell line in vitro drug response and patient’s in vivo drug response. We then applied these two drug prediction models to develop a personalized medicine approach in which the subsequent treatment depends on each patient’s gene-expression profile. Conclusion: The proposed method is much better than the existing approach and can capture a more accurate reflection of the relationship between genotypes and phenotypes.

scholarly journals The novel ZEB1-upregulated protein PRTG induced by Helicobacter pylori infection promotes gastric carcinogenesis through the cGMP/PKG signaling pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Tian Xiang ◽  
Chunhui Yuan ◽  
Xia Guo ◽  
Honghao Wang ◽  
Qinzhen Cai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Signaling Pathway ◽  
Mouse Models ◽  
Tumor Bearing Mouse ◽  
Gastric Cancer Cells ◽  
Tumor Bearing ◽  
H Pylori

AbstractHelicobacter pylori (H. pylori) is listed as a class I carcinogen in human gastric cancer; however, the underlying mechanisms are poorly understood. In this study, we identified Protogenin (PRTG) was upregulated in both gastric cancer tissues and H. pylori-infected tissues by analyzing dysregulated genes in TCGA and GEO databases. Importantly, upregulated PRTG predicted poor prognosis of gastric cancer patients and integrative analysis revealed that PRTG served as an oncogenic protein in gastric cancer and was required for H. pylori-mediated tumorigenic activities in in vitro cellular and in vivo tumor-bearing mouse models. Mechanistically, H. pylori infection enhanced PRTG expression by promoting transcriptional factor ZEB1 stabilization and recruitment to the PRTG promoter, and which then activated the sub-following cGMP/PKG signaling pathway in bioinformatic and cellular studies. Cellular studies further confirmed that PRTG depended on activating cGMP/PKG axis to promote proliferation, metastasis, and chemoresistance of gastric cancer cells. The PKG inhibitor KT5823 played synergistic anti-tumor effects with cisplatin and paclitaxel to gastric cancer cells in in vitro cellular and in vivo tumor-bearing mouse models. Taken together, our findings suggested that H. pylori infection depends on ZEB1 to induce PRTG upregulation, and which leading to the development and progression of gastric cancer through activating cGMP/PKG signaling pathway. Blocking PRTG/cGMP/PKG axis, therefore, presents a promising novel therapeutic strategy for gastric cancer.

scholarly journals Shedding Light on the African Enigma: In Vitro Testing of Homo sapiens-Helicobacter pylori Coevolution

2021 ◽  
Vol 9 (2) ◽  
pp. 240
Author(s):  
Bruno Cavadas ◽  
Marina Leite ◽  
Nicole Pedro ◽  
Ana C. Magalhães ◽  
Joana Melo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Host Response ◽  
Homo Sapiens ◽  
European Ancestry ◽  
Genome Wide ◽  
Expression Host ◽  
H Pylori ◽  
Human Ancestry

The continuous characterization of genome-wide diversity in population and case–cohort samples, allied to the development of new algorithms, are shedding light on host ancestry impact and selection events on various infectious diseases. Especially interesting are the long-standing associations between humans and certain bacteria, such as the case of Helicobacter pylori, which could have been strong drivers of adaptation leading to coevolution. Some evidence on admixed gastric cancer cohorts have been suggested as supporting Homo-Helicobacter coevolution, but reliable experimental data that control both the bacterium and the host ancestries are lacking. Here, we conducted the first in vitro coinfection assays with dual human- and bacterium-matched and -mismatched ancestries, in African and European backgrounds, to evaluate the genome wide gene expression host response to H. pylori. Our results showed that: (1) the host response to H. pylori infection was greatly shaped by the human ancestry, with variability on innate immune system and metabolism; (2) African human ancestry showed signs of coevolution with H. pylori while European ancestry appeared to be maladapted; and (3) mismatched ancestry did not seem to be an important differentiator of gene expression at the initial stages of infection as assayed here.

scholarly journals A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

2020 ◽  
Vol 14 ◽  
Author(s):  
Mette Soerensen ◽  
Dominika Marzena Hozakowska-Roszkowska ◽  
Marianne Nygaard ◽  
Martin J. Larsen ◽  
Veit Schwämmle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cognitive Functioning ◽  
Association Study ◽  
Gene Expression Data ◽  
Monozygotic Twins ◽  
Later Life ◽  
Expression Data ◽  
Genome Wide ◽  
A Genome
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