Epigenetic Mechanisms and Events in Gastric Cancer-Emerging Novel Biomarkers

Abstract

Gastric cancer is one of the most common malignancy worldwide. The various genetic and epigenetic events have been found to be associated with its carcinogenesis. The epigenetic is a heritable and transient/reversible change in the gene expression that is not accompanied by modification in the DNA sequence. This event is characterized by the alteration in the promoter CpG island of the gene or histone modification. These events are associated with silencing of critical tumor suppressor gene and activation of oncogenes leading to carcinogenesis. The DNA methylation is a chemical change in the DNA sequence that most commonly occurs at cytosine moiety of CpG dinucleotide and histone, primarily on N- terminal tail that ultimately effect the interaction of DNA with chromatin modifying protein.Hypermethylation of tumor suppressor genes and global hypomethylation of oncogenes are widely studied epigenetic modifications. There are large number of publish reports regarding epigenetic events involving gastric cancer. These changes are potentially useful in identifying markers for early diagnosis and management of this lethal malignancy. Also, role of specific miRNAs and long non coding RNAs in regulation of gene expression is gaining interest and is a matter of further investigation. In this review, we aimed to summarize major epigenetic events (DNA methylation) in gastric cancer along with alteration in miRNAs and long non coding RNAs which plays an important role in pathology of this poorly understood malignancy.

High‐level expression of PRSS3 correlates with metastasis and poor prognosis in patients with gastric cancer

“…26 Hypermethylation can inhibit transcription of promoter regions in tumor suppressor genes, by which downregulation or silencing of tumor suppressor gene expression is achieved, and hypomethylation can activate oncogene transcription. 8 In addition to their effect on transcription, methylation pattern changes can also influence the activity of the encoded proteins by affecting intergenic and intragenic DNA (eg, repeats and transposon elements) resulting in genetic insufficiency, instability, and mutation. 8 At present, genome hypomethylation is increasingly being researched.…”

“…8 In addition to their effect on transcription, methylation pattern changes can also influence the activity of the encoded proteins by affecting intergenic and intragenic DNA (eg, repeats and transposon elements) resulting in genetic insufficiency, instability, and mutation. 8 At present, genome hypomethylation is increasingly being researched. In chemical carcinogen-induced rat hepatocellular carcinoma nodules, hypomethylation of RAF, c-Myc, c-Los, c-HRAS, and c-KRAS promoter regions is associated with elevated protein expression levels.…”

“…The growth, invasion, and migration of GC are governed by an array of oncogenes, tumor suppressor genes, and genes related to cell cycle progression, DNA damage repair, and apoptosis. 7,8 The functional roles of these potential biomarkers in promoting metastasis of GC must be explored to generate new means of prognostic screening.…”

Combined detection of miR-21-5p, miR-30a-3p, miR-30a-5p, miR-155-5p, miR-216a and miR-217 for screening of early heart failure diseases

“…They play an important role in development, apoptosis, metabolism and human diseases. The physiological and pathological regulation mechanism of miRNA is a new discipline which has been highly valued in recent years [10][11][12].…”

Identification of the subtypes of gastric cancer based on DNA methylation and the prediction of prognosis

“…GC accounts for 20% of the burden of disability-adjusted life-years from cancer worldwide [ 31 ]. It is a cancer with complex genetic heterogeneity and because of this, the classification of GC using Lauren’s or other histological criteria is ignored when treating the subtypes [ 3 , 5 , 32 , 33 ]. Although cancer-related biomarkers and targeted drugs such as trastuzumab have been found and are used in clinical practice, the tumors are often inoperable when patients are diagnosed and can recur after resection [ 1 ].…”