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Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers.

Sandoval-Bórquez A, Saavedra K, Carrasco-Avino G, Garcia-Bloj B, Fry J, Wichmann I, Corvalán AH - Dis. Markers (2015)

Bottom Line: The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics.Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics.Potential biomarkers are appearing from analyses of noncoding genomics.

View Article: PubMed Central - PubMed

Affiliation: Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, 8330034 Santiago, Chile ; Scientific and Technological Bioresource Nucleus (BIOREN) and Graduate Program in Applied Cell and Molecular Biology, Universidad de La Frontera, 4811230 Temuco, Chile ; UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, 8330034 Santiago, Chile.

ABSTRACT
Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade.

No MeSH data available.


Related in: MedlinePlus

Marked increasing expression of miR-221, miR-376c, and miR-744 over time in 20 GC cases during 15-year (1989–2003) follow-up period. Error bars represent 95% CI (taken with permission from [103]).
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fig5: Marked increasing expression of miR-221, miR-376c, and miR-744 over time in 20 GC cases during 15-year (1989–2003) follow-up period. Error bars represent 95% CI (taken with permission from [103]).

Mentions: Four studies examined the potential role of miRNAs as noninvasive biomarkers for gastric cancer in the context of the gastric precancerous cascade [103–106]. Song et al. [103] investigated the potentiality of serum miRNAs as biomarkers for early detection of gastric cancer in a population-based study in Linqu, a high-risk area of GC in China. Differential miRNAs were identified in serum pools of GC and control and validated gastric cancer and dysplasia versus controls pairs, respectively. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in gastric cancer patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for noninvasive detection of gastric cancer in a 15-year follow-up period (Figure 5). Receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish gastric cancer with 82.4% sensitivity and 58.8% specificity. Fu et al. [104] detected the levels of circulating miR-222 in plasma of gastric cancer patients and evaluated its diagnostic value (Table 3). The result showed that the expression of circulating miR-222 in plasma was significantly upregulated in gastric cancer compared with AG and healthy controls (p < 0.001). ROC curve analyses revealed that miR-222 had a diagnostic accuracy of 0.850 with 66.1% sensitivity and 88.3% specificity. Liu et al., [105] examined the expression patterns of serum let-7 miR and its target gene, pepsinogen C (PGC) in gastric cancer, AG, and controls. The results showed that sera let-7c, let-7i, and let-7f demonstrated significant differences throughout the progression of the cascade (Table 4). The feasibility of using gastric juice was examined by Yu et al. [106]. Gastric cancer patients had significantly lower levels of gastric juice of miR-129-1-3p and miR-129-2-3p with an AUC of 0.639 and 0.651, respectively. Taken together, these results suggest that miRNAs play essential roles in gastric cancer at cell proliferation, cell cycle, and invasion/metastasis levels. In gastric precancerous conditions, miRNAs are linked with H. pylori-related gastritis and IM. MicroRNAs have strong potential as novel noninvasive biomarkers for gastric cancer risk assessment.


Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers.

Sandoval-Bórquez A, Saavedra K, Carrasco-Avino G, Garcia-Bloj B, Fry J, Wichmann I, Corvalán AH - Dis. Markers (2015)

Marked increasing expression of miR-221, miR-376c, and miR-744 over time in 20 GC cases during 15-year (1989–2003) follow-up period. Error bars represent 95% CI (taken with permission from [103]).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4563069&req=5

fig5: Marked increasing expression of miR-221, miR-376c, and miR-744 over time in 20 GC cases during 15-year (1989–2003) follow-up period. Error bars represent 95% CI (taken with permission from [103]).
Mentions: Four studies examined the potential role of miRNAs as noninvasive biomarkers for gastric cancer in the context of the gastric precancerous cascade [103–106]. Song et al. [103] investigated the potentiality of serum miRNAs as biomarkers for early detection of gastric cancer in a population-based study in Linqu, a high-risk area of GC in China. Differential miRNAs were identified in serum pools of GC and control and validated gastric cancer and dysplasia versus controls pairs, respectively. The miRNA profiling results demonstrated that 16 miRNAs were markedly upregulated in gastric cancer patients compared to controls. Further validation identified a panel of three serum miRNAs (miR-221, miR-744, and miR-376c) as potential biomarkers for noninvasive detection of gastric cancer in a 15-year follow-up period (Figure 5). Receiver operating characteristic (ROC) curve-based risk assessment analysis revealed that this panel could distinguish gastric cancer with 82.4% sensitivity and 58.8% specificity. Fu et al. [104] detected the levels of circulating miR-222 in plasma of gastric cancer patients and evaluated its diagnostic value (Table 3). The result showed that the expression of circulating miR-222 in plasma was significantly upregulated in gastric cancer compared with AG and healthy controls (p < 0.001). ROC curve analyses revealed that miR-222 had a diagnostic accuracy of 0.850 with 66.1% sensitivity and 88.3% specificity. Liu et al., [105] examined the expression patterns of serum let-7 miR and its target gene, pepsinogen C (PGC) in gastric cancer, AG, and controls. The results showed that sera let-7c, let-7i, and let-7f demonstrated significant differences throughout the progression of the cascade (Table 4). The feasibility of using gastric juice was examined by Yu et al. [106]. Gastric cancer patients had significantly lower levels of gastric juice of miR-129-1-3p and miR-129-2-3p with an AUC of 0.639 and 0.651, respectively. Taken together, these results suggest that miRNAs play essential roles in gastric cancer at cell proliferation, cell cycle, and invasion/metastasis levels. In gastric precancerous conditions, miRNAs are linked with H. pylori-related gastritis and IM. MicroRNAs have strong potential as novel noninvasive biomarkers for gastric cancer risk assessment.

Bottom Line: The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics.Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics.Potential biomarkers are appearing from analyses of noncoding genomics.

View Article: PubMed Central - PubMed

Affiliation: Advanced Center for Chronic Diseases (ACCDiS), Pontificia Universidad Católica de Chile, 8330034 Santiago, Chile ; Scientific and Technological Bioresource Nucleus (BIOREN) and Graduate Program in Applied Cell and Molecular Biology, Universidad de La Frontera, 4811230 Temuco, Chile ; UC-Center for Investigational Oncology (CITO), Pontificia Universidad Católica de Chile, 8330034 Santiago, Chile.

ABSTRACT
Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs), regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade.

No MeSH data available.


Related in: MedlinePlus