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Review
. 2020 Feb 12;11:90.
doi: 10.3389/fmicb.2020.00090. eCollection 2020.

Gastric Damage and Cancer-Associated Biomarkers in Helicobacter pylori-Infected Children

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Free PMC article
Review

Gastric Damage and Cancer-Associated Biomarkers in Helicobacter pylori-Infected Children

Sergio George et al. Front Microbiol. .
Free PMC article

Abstract

Helicobacter pylori (H. pylori) is well-known to be involved in gastric carcinogenesis, associated with deregulation of cell proliferation and epigenetic changes in cancer-related genes. H. pylori infection is largely acquired during childhood, persisting long-term in about half of infected individuals, a subset of whom will go on to develop peptic ulcer disease and eventually gastric cancer, however, the sequence of events leading to disease is not completely understood. Knowledge on carcinogenesis and gastric damage-related biomarkers is abundant in adult populations, but scarce in children. We performed an extensive literature review focusing on gastric cancer related biomarkers identified in adult populations, which have been detected in children infected with H. pylori. Biomarkers were related to expression levels (RNA or protein) and/or methylation levels (DNA) in gastric tissue or blood of infected children as compared to non-infected controls. In this review, we identified 37 biomarkers of which 24 are over expressed, three are under expressed, and ten genes are significantly hypermethylated in H. pylori-infected children compared to healthy controls in at least 1 study. Only four of these biomarkers (pepsinogen I, pepsinogen II, gastrin, and SLC5A8) have been studied in asymptomatically infected children. Importantly, 13 of these biomarkers (β-catenin, C-MYC, GATA-4, DAPK1, CXCL13, DC-SIGN, TIMP3, EGFR, GRIN2B, PIM2, SLC5A8, CDH1, and VCAM-1.) are consistently deregulated in infected children and in adults with gastric cancer. Future studies should be designed to determine the clinical significance of these changes in infection-associated biomarkers in children and their persistence over time. The effect of eradication therapy over these biomarkers in children if proven significant, could lead to modifications in treatment guidelines for younger populations, and eventually promote the development of preventive strategies, such as vaccination, in the near future.

Keywords: Helicobacter pylori; cancer biomarker; children; gastric cancer biomarker; gastric damage; oncogene.

Figures

FIGURE 1
FIGURE 1
Expression and methylation levels of biomarkers potentially related to gastric damage or oncogenesis in H. pylori infected children, classified according to biological function. Higher columns represent overexpression in infected children compared to non-infected controls. Lower columns represent underexpression (↓) and/or methylation (*).
FIGURE 2
FIGURE 2
Clinical samples used to analyze each biomarker (vertical axis), and molecules identified in each case (horizontal axis). Each biomarker identified in this review is represented by a circle. Upper half: biomarkers analyzed in blood or serum. Lower half: biomarkers analyzed in gastric tissue. Right half: Biomarkers identified as proteins. Left half: biomarkers identified as RNA or DNA. Genes (DNA) in which methylation levels were analyzed are surrounded by a dashed rectangle.
FIGURE 3
FIGURE 3
Proposed natural evolution of H. pylori infection and biomolecular changes from asymptomatic childhood infection to adult gastric diseases. Interaction between factors related to the environment, the host and the pathogen may influence persistence H. pylori of infection, biomolecular changes in gastric cells and blood and the future development of benign and malign gastric disease.

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