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Review
. 2020 Oct 7;12(10):2880.
doi: 10.3390/cancers12102880.

Non-Invasive Early Molecular Detection of Gastric Cancers

Hiroyuki Yamamoto  1 , Yoshiyuki Watanabe  1   2 , Yoshinori Sato  1 , Tadateru Maehata  1 , Fumio Itoh  1
Affiliations
Review

Non-Invasive Early Molecular Detection of Gastric Cancers

Hiroyuki Yamamoto et al. Cancers (Basel). .

Abstract

Gastric cancer (GC) is a significant source of global cancer death with a high mortality rate, because the majority of patients with GC are diagnosed at a late stage, with limited therapeutic choices and poor outcomes. Therefore, development of minimally invasive or noninvasive biomarkers which are specific to GC is crucially needed. The latest advancements in the understanding of GC molecular landscapes and molecular biological methods have accelerated attempts to diagnose GC at an early stage. Body fluids, including peripheral blood, saliva, gastric juice/wash, urine, and others, can be a source of biomarkers, offering new methods for the early detection of GC. Liquid biopsy-based methods using circulating sources of cancer nucleic acids could also be considered as alternative strategies. Moreover, investigating gastric juices/washes could represent an alternative for the detection of GC via invasive biopsy. This review summarizes recently reported biomarkers based on DNA methylation, microRNA, long noncoding RNA, circular RNA, or extracellular vesicles (exosomes) for the detection of GC. Although the majority of studies have been conducted to detect these alterations in advanced-stage GC and only a few in population studies or early-stage GC, some biomarkers are potentially valuable for the development of novel approaches for an early noninvasive detection of GC.

Keywords: DNA methylation; circular RNA; extracellular vesicles; gastric juice; gastric wash; liquid biopsy; long noncoding RNA; microRNA.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Molecular alterations in gastric carcinogenesis. The model for gastric carcinogenesis is presented based on alterations in genome, epigenome, and noncoding RNAs. Methylation of the genes in blue appears to be involved in an epigenetic field defect. H. pylori: Helicobacter pylori; MSI-H: High- frequency microsatellite instability; EBV: Epstein–Barr virus.
Figure 2
Figure 2
Molecular targets with the potential as diagnostic biomarkers for gastric cancer (GC). Upregulated (in red) and downregulated (in blue) markers are shown. Sensitivity and specificity are shown in square brackets.
Figure 3
Figure 3
Potential applications of liquid biopsies during the course of GC management. Evidence level is shown.
Figure 4
Figure 4
miRNAs potentially considered as diagnostic biomarkers for GC. Upregulated (in red) and downregulated (in blue) miRNAs are shown. Sensitivity and specificity are shown in square brackets. PLF: peritoneum lavage fluid.
Figure 5
Figure 5
Origins and range of alterations in liquid biopsies. Left bottom, cell-free DNA (cfDNA) predominantly consists of nucleosome-protected DNA shed into the bloodstream by cells undergoing apoptosis.
Figure 6
Figure 6
Gastric juice (GJ)-based molecular targets potentially considered as diagnostic biomarkers for GC. Upregulated (in red) and downregulated (in blue) markers are shown. Sensitivity and specificity are shown in square brackets.
Figure 7
Figure 7
Gastric wash (GW)-based molecules with the potential as diagnostic biomarkers for GC. Sensitivity and specificity are shown in square brackets.
See this image and copyright information in PMC

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