Chronic inflammation and long-lasting changes in the gastric mucosa after Helicobacter pylori infection involved in gastric cancer

Yang, Hang; Wei, Bin; Hu, Bing

doi:10.1007/s00011-021-01501-x

Cited by 23 publications

(20 citation statements)

References 143 publications

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“…Spasmolytic polypeptide-expressing metaplasia is usually reversible, and IM seems to have a “point of no return” [ 6 ]. Additionally, chronic inflammation and other long-lasting changes in the gastric mucosa caused by H. pylori infection, such as mitochondrial changes, senescence, (epi)genetic alterations, and dysbiosis of gastric microbiome, contribute to GC independent of H. pylori [ 9 ]. In clinical practice, surveillance every 3 years is recommended in patients with atrophy and/or IM affecting both antral and corpus mucosa or at OLGA/OLGIM III/IV stage [ 102 , 103 ].…”

Section: Problems After Eradication Treatmentmentioning

confidence: 99%

“…Immunologically, it can evade host immune clearance and persistently colonize the niches, ultimately leading to the activation of pattern recognition receptors on antigen-presenting cells, gastric epithelial cells, and neutrophils [ 7 ]. In addition, H. pylori induces the activation of NF- κ B of gastric epithelial cells and leukocytes [ 7 ], contributing to the long-term colonization of H. pylori , chronic inflammatory microenvironment, and abnormal apoptosis, which further leads to accumulating mutations and malignant transformation of gastric epithelial cells [ 8 , 9 ]. However, senescence associated with aging and chronic inflammation may contribute to the neoplastic transformation [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, H. pylori induces the activation of NF- κ B of gastric epithelial cells and leukocytes [ 7 ], contributing to the long-term colonization of H. pylori , chronic inflammatory microenvironment, and abnormal apoptosis, which further leads to accumulating mutations and malignant transformation of gastric epithelial cells [ 8 , 9 ]. However, senescence associated with aging and chronic inflammation may contribute to the neoplastic transformation [ 9 , 10 ]. Oncoprotein cytotoxin-associated gene A ( CagA ) is also a dominant factor leading to GC and activates oncogenic signaling pathways and inactivates tumor suppressors [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Detection and Treatment of Helicobacter pylori: Problems and Advances

Yang

Guan

2022

Gastroenterology Research and Practice

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Helicobacter pylori (H. pylori) infection is chronic and etiologically linked to gastric cancer (GC) derived from gastric epithelium. The potential mechanism is complex, covering chronic inflammation, epithelial senescence, NF-κB activation, the cytotoxin-associated gene A protein translocation, and related abnormal signaling pathways. In clinical practice, the test-and-treat strategy, endoscopy-based strategy, and (family-based) screen-and-treat strategy are recommended to detect H. pylori and prevent GC. It has been demonstrated that the decreasing annual incidence of GC is largely attributable to the management of H. pylori. This study reviews the current clinical practice of H. pylori on the detection and eradication, alternative treatment strategies, and related problems and advances, and hopes to contribute to the better clinical management of H. pylori.

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Section: Problems After Eradication Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Detection and Treatment of Helicobacter pylori: Problems and Advances

Yang

Guan

2022

Gastroenterology Research and Practice

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“…Chronic inflammation largely orchestrates the tumor microenvironment and hence greatly contributes to GC carcinogenesis, particularly the intestinal-type GC (3)(4)(5). According to pathology and epidemiology evidence, intestinaltype GC rather than diffuse-type GC is usually triggered by chronic superficial gastritis (SG), atrophy gastritis (AG), intestinal metaplasia (IM), and dysplasia in that order, whose progress may stretch over decades (6,7), indicating the crucial roles of the inflammation-carcinoma sequence in intestinal-type GC carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

The emerging double-edged sword role of Sirtuins in the gastric inflammation-carcinoma sequence revealed by bulk and single-cell transcriptomes

Wang

et al. 2022

Front. Oncol.

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Histone modification and the inflammation-carcinoma sequence (ICS) have been acknowledgedly implicated in gastric carcinogenesis. However, the extremum expression of some histone modification genes (HMGs) in intestinal metaplasia (IM) rather than GC obscures the roles of HMGs in ICS. In this study, we assumed an explanation that the roles of HMGs in ICS were stage specific. Bulk RNA-seq on endoscopy biopsy samples from a total of 50 patients was accompanied by reanalysis of a set of published single-cell transcriptomes, which cross-sectionally profiled the transcriptomic features of chronic superficial gastritis (SG), atrophy gastritis (AG), IM, and early gastric cancer (GC). Differential analysis observed significantly peaked expression of SIRT6 and SIRT7 at IM. Weighted correlation network analysis on bulk transcriptome recognized significant correlations between SIRT1/6 and IM. The single-cell atlas identified one subgroup of B cells expressing high level of TFF1 (TFF1hi naive B cell) that theoretically played important roles in defending microbial infection, while SIRT6 displayed a positive correlation with TFF1low naive B cells. Moreover, gene set enrichment analysis at different lesions (SG-AG, AG-IM, and IM-GC) highlighted that gene sets contributing to IM, e.g., Brush Border, were largely enriched from co-expressing genes of Sirtuins (SIRTs) in AG-IM. Surveys of the genes negatively correlated with SIRT6 in public databases considered SIRT6 as tumor suppressors, which was confirmed by the cell proliferation and migration assays after transient transfection of SIRT6 overexpression vector into AGS cells. All the above observations were then confirmed by serial section-based immunohistochemistry against Ki-67, MUC2, MUC5AC, p53, and SIRT6 on the endoscopic submucosal dissection tissue. By contrast, the expression of the other HMGs varied even opposite within same family. Taken together, this study preliminarily demonstrated the two-edged sword role of SIRTs in ICS and, by extension, showed that the roles of HMGs in ICS were probably stage specific. Our study may provide new insights into and attract attention on gastric prevention and therapy targeting HMGs.

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“…Helicobacter pylori ( H. pylori ) is almost the exclusive cause of gastric cancers 1 , 2 , and H. pylori -triggered chronic inflammation is deeply involved in gastric carcinogenesis 3 – 6 . At the molecular level, aberrant DNA methylation is strongly induced by H. pylori infection-triggered chronic inflammation long before cancer development 7 , 8 .…”

Section: Introductionmentioning

confidence: 99%

Comparable genetic alteration profiles between gastric cancers with current and past Helicobacter pylori infection

Tsuyuki

Takeshima²,

Sekine³

et al. 2021

Sci Rep

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Gastric cancers can develop even after Helicobacter pylori (H. pylori) eradication in 0.2–2.9% cases per year. Since H. pylori is reported to directly activate or inactivate cancer-related pathways, molecular profiles of gastric cancers with current and past H. pylori infection may be different. Here, we aimed to analyze whether profiles of point mutation and gene amplification are different between the two groups. Current or past infection by H. pylori was determined by positive or negative amplification of H. pylori jhpr3 gene by PCR, and past infection was established by the presence of endoscopic atrophy. Among the 90 gastric cancers analyzed, 55 were with current infection, and 35 were with past infection. Target sequencing of 46 cancer-related genes revealed that 47 gastric cancers had 68 point mutations of 15 different genes, such as TP53 (36%), KRAS (4%), and PIK3CA (4%) and that gene amplification was present for ERBB2, KRAS, PIK3CA, and MET among the 26 genes assessed for copy number alterations. Gastric cancers with current and past infection had similar frequencies of TP53 mutations (38% and 31%, respectively; p = 0.652) and oncogene activation (20% and 29%, respectively; p = 0.444). Gastric cancers with current and past infection had comparable profiles of genetic alterations.

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Chronic inflammation and long-lasting changes in the gastric mucosa after Helicobacter pylori infection involved in gastric cancer

Cited by 23 publications

References 143 publications

Detection and Treatment of Helicobacter pylori: Problems and Advances

Detection and Treatment of Helicobacter pylori: Problems and Advances

The emerging double-edged sword role of Sirtuins in the gastric inflammation-carcinoma sequence revealed by bulk and single-cell transcriptomes

Comparable genetic alteration profiles between gastric cancers with current and past Helicobacter pylori infection

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