Active matrix metalloproteases are expressed early on and are high during the Barrett’s esophagus malignancy sequence

Davelaar, Akueni L.; Straub, Daniëlle; Buttar, Navtej; Fockens, Paul; Krishnadath, Kausilia K.

doi:10.3109/00365521.2014.940379

Cited by 15 publications

(17 citation statements)

References 44 publications

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“…These genes included several members of the matrix metalloproteinases (MMPs) family; MMP1, MMP7, MMP12, MMP3, and MMP10. MMPs overexpression has been described in several cancers including EACs, and their activation is associated with matrix remodeling, invasion and angiogenesis2699. We also detected DNA hypomethylation and overexpression of SPP1 and LYN.…”

Section: Resultssupporting

confidence: 54%

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Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

Peng

Guo

Chen

et al. 2017

Sci Rep

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The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, bioinformatics analysis detected a prominent K-RAS signature and predicted activation of several important transcription factor networks, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. Notably, we detected hypomethylation and overexpression of several pro-inflammatory genes such as COX2, IL8 and IL23R, suggesting an important role of epigenetic regulation of these genes in the inflammatory cascade associated with EAC. In summary, this integrative analysis demonstrates a complex interaction between genetic and epigenetic mechanisms providing several novel insights for our understanding of molecular events in EAC.

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Section: Resultssupporting

confidence: 54%

“…For example, we identified two upregulated GO categories related to metallopeptidase. Aberrant expression of these proteins has been associated with esophageal adenocarcinomas252627. Our finding suggests that the differential expression of metalloproteinases related genes is important for EAC.…”

Section: Resultsmentioning

confidence: 52%

Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

Peng

Guo

Chen

et al. 2017

Sci Rep

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“…We found this protease increased although our group of patients with BE did not show dysplasia. [13] Further studies are required to determine if metalloproteins play a role in mucosal damage in BE. Our study highlights the participation of MMP-9 and MMP-3 in patients with BE, possibly forming part of their pathological mechanism for this change of epithelium.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of Inflammatory Cytokines in Esophageal Biopsies of Different Phenotypes of Gastroesophageal Reflux Disease: a cross-sectional study.

Zavala-Solares

Fonseca‐Camarillo

Valdovinos

et al. 2020

Preprint

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Background: Patients clinical endoscopic phenotypes in gastroesophageal reflux disease (GERD) are classified as: Barrett's esophagus (BE), erosive esophagitis (EE) and non-erosive gastroesophageal reflux disease (NERD). NERD are subclassified in Abnormal acid exposure (AAE) and Normal acid exposure (NAE) according to pH monitoring study. The aim of this study was to characterize genes involved in the pathophysiology and immune response of GERD.Methods: This is an observational and cross-sectional study. All patients with BE, EE, AAE, NAE and control group were subjected to a superior endoscopy (with biopsies of esophageal mucosa). The cytokine mRNA relative quantification of target genes was conducted by RT-PCR. Changes in gene expression were assessed of the genes associated with inflammation in each disease phenotype. Statistical analysis of differential gene expression was performed by using Dunn's Multiple Comparison non-parametric test. A p value < 0.05 was considered as significant. Results: A total of 82 patients were included and they were divided into the following groups: Group BE 16 (19.51%), Group EE 23 (28.04%), Group AAE 13 (15.86%), NAE (15.86%) and Control Group 17 (20.73%). When comparing with control group we found: patients with BE showed an increased expression of IL-8 (P<0.005) and higher levels of: IL-10 and MMP-3, MMP-9 as well; patients with EE had higher levels of IL-1B, IL-6 and IL-10 (P<0.005), patients with AAE showed an increased expression of Il-1B, Il-6, IFN-γ and TNF-α (P<0.005). AAE had a higher expression of Il-1B and TNF-α than NAE (P<0.005). Conclusions: This study demonstrates the differential expression of mediators of inflammation in the esophageal mucosa of patients in GERD endoscopic phenotypes. MMP3 could be implicated in damage to esophageal mucosa. IL-1B and TNF-α could be a differential diagnosis between AAE and NAE in the non-erosive phenotype from endoscopic biopsies.

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“…Furthermore, mouse reflux models yield much lower incidence of BE as compared to rat reflux models even with the addition exogenous carcinogens. Novel surgical approaches like recently published by Davelaar et al 50 have the potential to overcome this impediment and are described in detail below. We have divided the mouse models below, based on the approach used.…”

Section: Mice Modelsmentioning

confidence: 99%

“…Davelaar et al 50 recently developed a novel suture-less method to create a side-to-side EJ model by implantation of neodymium micromagnets in both esophagus and jejunum which then oppose to fistulate within days by pressure necrosis. This approach causes significantly lesser morbidity and mortality in mice.…”

Section: Purely Surgical Modelsmentioning

confidence: 99%

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past, Present, and Future

Kapoor

Lohani

Lee

et al. 2015

Clinical Translational Sci

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Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long-standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with five-year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett's esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett's esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review article, we critically examined the current animal models of Barrett's esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett's carcinogenesis.

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Active matrix metalloproteases are expressed early on and are high during the Barrett’s esophagus malignancy sequence

Cited by 15 publications

References 44 publications

Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

Gene Expression Profiling of Inflammatory Cytokines in Esophageal Biopsies of Different Phenotypes of Gastroesophageal Reflux Disease: a cross-sectional study.

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past, Present, and Future

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