Molecular Alterations in Gastric Intestinal Metaplasia

Abstract

Gastric cancer (GC) remains one of the most common causes of mortality worldwide. Intestinal metaplasia (IM) is one of the preneoplastic gastric lesions and is considered an essential predisposing factor in GC development. Here we present a review of recent most relevant papers to summarize major findings on the molecular alterations in gastric IM. The latest progress in novel diagnostic methods allows scientists to identify various types of molecular alterations in IM, such as polymorphisms in various genes, changes in the expression of micro-RNAs and long noncoding RNAs, and altered microbiome profiles. The results have shown that some of these alterations have strong associations with IM and a potential to be used for screening, treatment, and prognostic purposes; however, one of the most important limiting factors is the inhomogeneity of the studies. Therefore, further large-scale studies and clinical trials with standardized methods designed by multicenter consortiums are needed. As of today, various molecular alterations in IM could become a part of personalized medicine in the near future, which would help us deliver a personalized approach for each patient and identify those at risk of progression to GC.

Gastric epithelial histology and precancerous conditions

“…Factors affecting gene expression, including mutations, DNA methylation and SNPs, as well as epigenetic factors, including microRNAs, long noncoding RNAs and mRNAs, have been associated with IM and have a potential role in screening, treatment and prognostic purposes[ 119 ]. IM patients with shortened telomeres and chromosomal alterations were likely to develop subsequent dysplasia or GC, whereas patients exhibiting normal epigenetic patterns were likely to experience regression.…”

Analyzing Modern Biomolecules: The Revolution of Nucleic-Acid Sequencing – Review

“…Interestingly, these findings are particularly relevant for personalized treatments of complex diseases, such as cancer, diabetes and asthma, as well as chronic age-related diseases, due to the interaction of multiple genetic and environmental factors [13,163,164]. Indeed, new sequencing technologies have allowed epigenetic profiling of different cancers [78,165]. It has been proposed that DNA methylation of probiotics plays an important role in immune responses of allergies, autoimmune disorders and cancer.…”

“…This is contributing to identify healthy microbiomes, as well as diseases linked to dysbiosis scenarios [181]. Altered microbiome profiles have been found in many diseases, not only for typical infections, but also for other disfunctions, such as cancer [165,182]. Nevertheless, results obtained in different experiments may be different, due to experimental biases that must be properly addressed [183].…”

MTRR rs1532268 polymorphism and gastric cancer risk: evidence from a meta-analysis

“…In addition, some of these alterations may be used for screening, treatment, and prognostic predictions. 4 Polymorphisms in several genes were found to be associated with GC, such as DAL-1, Mucin, TLR2, MTR, TP73, and TP53 , 5 – 6 and a prognostic model of GC was built according to the analysis of gene polymorphisms. 7 …”

“…In addition, some of these alterations may be used for screening, treatment, and prognostic predictions. 4 Polymorphisms in several genes were found to be associated with GC, such as DAL-1, Mucin, TLR2, MTR, TP73, and TP53, [5][6] and a prognostic model of GC was built according to the analysis of gene polymorphisms. 7 The methionine synthase reductase (MTRR) gene is positioned on the short arm of chromosome 5 (region 5p15.2 to 15.3) and encodes the MTRR enzyme involved in the metabolic pathway of homocysteine.…”