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

Abstract

Helicobacter pylori (H. pylori) is well-known to be involved in gastric carcinogenesis, associated with deregulation of cell proliferation and epigenetic changes in cancerrelated 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.

Predictive Effect of Helicobacter pylori in Gastric Carcinoma Development: Systematic Review and Quantitative Evidence Synthesis

“…Conversely, to the inflammatory model, more recent findings demonstrate that several tumor suppressor genes are consistently downregulated among children diagnosed with H. pylori [24,25]. This finding suggests there may be other potential pathways in which H. pylori infection can cause malignancy, emphasizing the greater motivation for continued follow-up, screenings, and/or treatment of infected children.…”

Combining Genetic Mutation and Expression Profiles Identifies Novel Prognostic Biomarkers of Lung Adenocarcinoma

“…To reveal how the DMGs impact their expression levels is one of our future works. From the KM plots of the DMGs, GRIN2B is a potential tumor suppressor gene in LUAD, which has been confirmed in some types of cancer, such as diffuse large B-cell lymphoma, 48 gastric cancer, 47 and LUAD. 49 There are 2 main limitations of this study.…”

Characterization of the Immune Response in Patients Infected with Clostridioides Difficile Due to Serum Biomarkers' Level with Correlation to Clinical Characteristics and Bacterial Toxin Production

“…To the best of our knowledge, our study is the rst that shows that serum BCA-1 levels are associated with CDI severity. Previous studies have shown association in infected children with helicobacter pylori and in adults with gastric cancer [20]. Other studies reported a poor prognosis in a few types of cancer include gastric cancer and prostate cancer [21,22].…”