One stomach, two subtypes of carcinoma—the differences between distal and proximal gastric cancer

Zhang, Yuan; Zhang, Pengshan; Rong, Zeyin; Huang, Chen

doi:10.1093/gastro/goab050

Cited by 15 publications

(8 citation statements)

References 143 publications

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“…To our knowledge, the present study reports the largest genomic and transcriptional survey of human IMs to date. Similar to GCs, IMs can involve different stomach regions, with IMs tending to originate in the antrum due to Hp infection [54].…”

Section: Discussionmentioning

confidence: 99%

Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression

Huang

Uchihara

et al. 2023

Preprint

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Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We analyzed 1256 gastric samples (1152 IMs) from 692 subjects through a prospective 10-year study. We identified 26 IM driver genes in diverse pathways including chromatin regulation (ARID1A) and intestinal homeostasis (SOX9), largely occurring as small clonal events. Analysis of clonal dynamics between and within subjects, and also longitudinally across time, revealed that IM clones are likely transient but increase in size upon progression to dysplasia, with eventual transmission of somatic events to paired GCs. Single-cell and spatial profiling highlighted changes in tissue ecology and lineage heterogeneity in IM, including an intestinal stem-cell dominant cellular compartment linked to early malignancy. Expanded transcriptome profiling revealed expression-based molecular subtypes of IM, including a body-resident "pseudoantralized" subtype associated with incomplete histology, antral/intestinal cell types, ARID1A mutations, inflammation, and microbial communities normally associated with the healthy oral tract. We demonstrate that combined clinical-genomic models outperform clinical-only models in predicting IMs likely to progress. Our results raise opportunities for GC precision prevention and interception by highlighting strategies for accurately identifying IM patients at high GC risk and a role for microbial dysbiosis in IM progression.

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Section: Discussionmentioning

confidence: 99%

Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression

Huang

Uchihara

et al. 2023

Preprint

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“…It is noteworthy that, while GERD is a risk factor for esophageal cancer development ( 50 ), epidemiological studies have not found an association between EoE and esophageal cancer, despite the presence of chronic inflammation ( 51 ). In contrast, reflux has been shown to influence other esophageal conditions such as achalasia and scleroderma, which are both associated with a higher susceptibility to esophageal cancer progression ( 52 , 53 ). Therefore, further exploration of the cellular landscape of EEC in GERD, with a larger cohort of patients, may provide valuable insights into the distinctions among GERD, EoE, achalasia, and scleroderma esophageal diseases and their varying susceptibilities to esophageal cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Suprabasal cells retain progenitor cell identity programs in eosinophilic esophagitis–driven basal cell hyperplasia

Clevenger,

Karami,

Carlson

et al. 2023

JCI Insight

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Eosinophilic esophagitis (EoE) is an esophageal immune-mediated disease characterized by eosinophilic inflammation and epithelial remodeling, including basal cell hyperplasia (BCH). Although BCH is known to correlate with disease severity and with persistent symptoms in patients in histological remission, the molecular processes driving BCH remain poorly defined. Here, we demonstrate that BCH is predominantly characterized by an expansion of nonproliferative suprabasal cells that are still committed to early differentiation. Furthermore, we discovered that suprabasal and superficial esophageal epithelial cells retain progenitor identity programs in EoE, evidenced by increased quiescent cell identity scoring and the enrichment of signaling pathways regulating stem cell pluripotency. Enrichment and trajectory analyses identified SOX2 and KLF5 as potential drivers of the increased quiescent identity and epithelial remodeling observed in EoE. Notably, these alterations were not observed in gastroesophageal reflux disease. These findings provide additional insights into the differentiation process in EoE and highlight the distinct characteristics of suprabasal and superficial esophageal epithelial cells in the disease.

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“…Intestinal GC is common in developing countries and results from the transformation of precancerous lesions such as chronic superficial gastritis to atrophic gastritis, intestinal metaplasia, and dysplasia into cancer. Diffuse GC is a non-differentiated form in which the tumor cells are disorganized, have less glandular structure, and are not associated with precancerous lesions [ 10 ]. The pathogenicity of H. pylori is increased due to factors that induce apoptosis and cell proliferation.…”

Section: Introductionmentioning

confidence: 99%

Performance of DNA Methylation on the Molecular Pathogenesis of Helicobacter pylori in Gastric Cancer; targeted therapy approach

et al. 2022

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Gastric cancer (GC) is a significant cause of cancer mortality which has led to focused exploration of the pathology of GC. The advent of genome-wide analysis methods has made it possible to uncover genetic and epigenetic fluctuation such as abnormal DNA methylation in gene promoter regions that is expected to play a key role in GC. The study of gastric malignancies requires an etiological perspective, and Helicobacter pylori (H. pylori) was identified to play a role in GC. H. pylori infection causes chronic inflammation of the gastric epithelium causing abnormal polyclonal methylation, which might raise the risk of GC. In the last two decades, various pathogenic factors by which H. pylori infection causes GC have been discovered. Abnormal DNA methylation is triggered in several genes, rendering them inactive. In GC, methylation patterns are linked to certain subtypes including microsatellite instability. Multiple cancer-related processes are more usually changed by abnormal DNA methylation than through mutations, according to current general and combined investigations. Furthermore, the amount of acquired abnormal DNA methylation is heavily linked to the chances of developing GC. Therefore, we investigated abnormal DNA methylation in GC and the link between methylation and H. pylori infection.

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One stomach, two subtypes of carcinoma—the differences between distal and proximal gastric cancer

Cited by 15 publications

References 143 publications

Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression

Spatiotemporal Genomic Profiling of Intestinal Metaplasia Reveals Clonal Dynamics of Gastric Cancer Progression

Suprabasal cells retain progenitor cell identity programs in eosinophilic esophagitis–driven basal cell hyperplasia

Performance of DNA Methylation on the Molecular Pathogenesis of Helicobacter pylori in Gastric Cancer; targeted therapy approach

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