angiotensinogen and Stomach-Neoplasms

The present study aims to identify aberrantly methylated and differentially expressed genes (DEGs) in gastric cancer (GC) and explore their potential role in the carcinogenesis and development of GC.. The original RNA-Seq, clinical information and Illumina Human Methylation 27 Chip data associated with GC were downloaded from The Cancer Genome Atlas (TCGA) database using the gdc-client tool. The DEGs and aberrantly methylated genes (AMGs) were screened with edgeR and limma package in R, respectively. The cut-off criteria for DEG identification were P < 0.05 and fold change (FC) >2.0, and for AMG identification were P < 0.05 and |t|>2.0. Genes which were both DEGs and AMGs were considered to be regulated by aberrant DNA methylation in GC. The common genes were used for further functional enrichment analysis in the categories of cellular component, molecular function, biological process and biological pathway.. In total 465 genes including 336 down-regulated genes with hyper-methylation (DGs-Hyper) and 129 up-regulated genes with hypo-methylation (UGs-Hypo) were identified. Cellular component analysis showed that these genes were mainly expressed in the cytoplasm and plasma membrane. Molecular function and biological process analysis indicated that the genes primarily participate in cell communication, signal transduction, cell growth/maintenance and function as transcription factors, receptor, cell adhesion molecules, and transmembrane receptor protein tyrosine kinases. Biological pathway analysis revealed that the genes are involved in some crucial pathways including epithelial-to-mesenchymal transition, IL3-mediated signaling, mTOR signaling, VEGF/VEGFR and c-Met signaling. KRT15, INHBA, MATN3, and AGT are significantly associated with the prognosis of GC patients.. Our study identified several DEGs regulated by aberrant DNA methylation in GC. The mechanism of DNA methylation in the carcinogenesis and development of GC could be further explored in these genes, especially KRT15, INHBA, MATN3, and AGT.

Topics: Adult; Aged; Angiotensinogen; Biomarkers, Tumor; Computational Biology; Databases, Genetic; DNA Methylation; Female; Humans; Inhibin-beta Subunits; Keratin-15; Male; Matrilin Proteins; Middle Aged; Prognosis; Stomach Neoplasms; Transcriptome

The renin-angiotensin (RA) system including angiotensinogen (AGT), angiotensin I and angiotensin II influences the regulation of cell proliferation, angiogenesis and inflammation. AGT-20 A/C polymorphism is associated with the plasma AGT and angiotensin II levels. The aim of this study was to clarify the association of AGT-20 A/C polymorphism with susceptibility to gastric cancer and peptic ulcer in Japanese.. We assessed the AGT-20 A/C polymorphism in Helicobacter pylori-positive patients with gastric cancer (n = 135), gastric ulcer (n = 148) and duodenal ulcer (n = 113) and controls (n = 292) consisting of H.pylori-positive gastritis alone (n = 160) and H.pylori-negative subjects (n = 132).. The age- and sex-adjusted odds ratios (ORs) of AGT-20 A/C and C/C genotypes relative to A/A genotype for gastric cancer risk were 1.695 [95% confidence interval (CI): 1.035-2.777] and 2.259 (95% CI: 0.351-14.533), respectively. The AGT-20 C allele increased the gastric cancer risk (OR: 1.685, 95% CI: 1.037-2.736), especially the intestinal type of gastric cancer (OR: 1.792, 95% CI: 1.040-3.089). However, there was no association between the AGT-20 polymorphism and susceptibility to peptic ulcer.. The carriage of AGT-20 C allele was associated with an increased risk for H.pylori-related gastric cancer development in Japanese, indicating that the RA system plays an important role in the pathogenesis of gastric cancer.

Topics: Aged; Angiotensinogen; Cell Division; Confidence Intervals; DNA; DNA, Neoplasm; Female; Genotype; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Odds Ratio; Pepsinogen A; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Stomach Neoplasms