Project description:Background: Intestinal metaplasia (IM) is a gastric precancerous lesion that precedes the development of gastric cancer in up to 3.77 cases/1000 person-years. It consists in a trans-differentiation process of gastric to intestinal tissue. Two histological subtypes exist, complete (CIM) and incomplete (IIM), the latter having higher progression rates to gastric cancer . Our objective was to identify molecular processes responsible for the tumoral transition from intestinal metaplasia to GC and the initial steps of this lesion Methods: We used expression microarray to compare the transcriptome of intestinal metaplasia subtypes that progress to gastric cancer (IIM-GC and CIM-GC) after a follow-up period with respect to those that do not progress (IIM control and CIM control). Also, IM-NoGC (IM control, comprising both IIM and CIM Control) was compared with healthy gastric mucosa. Differentially expressed genes were obtained and functional analyses (GSEA and IPA softwares) were performed. Some deregulated genes were validated by qPCR. Results: Histological subtypes of intestinal metaplasia that progress or not to GC differ less among them than to healthy mucosa. Incomplete intestinal metaplasia has a higher number of over-expressed carcinogenic genes and molecular processes than the complete subtype. Most relevant molecular processes and genes in this group include antigenic processing, inflammation, activation of cell cycle and cell proliferation, oncogenes and tumor suppressors. When IM-NoGC is compared with healthy gastric mucosa new identified transcripts include TRIM, TMEM, homeobox, transporters and nucleolar RNAs SNORDs116. We confirm previously reported processes such us intestinal differentiation, metabolism of lipids and of xenobiotics and identify new ones such as non tumoral Warburg effect and melatonin degradation. Conclusions: Differentially expressed genes and molecular processes have been identified for the first time in intestinal metaplasia that progress to gastric cancer. New genes and molecular processes have also been identified in intestinal metaplasia in comparison with healthy gastric mucosa.
Project description:Metaplasia of the gastric epithelia (intestinal metaplasia, IM) is a pre-malignant lesion associated with increased gastric cancer (GC) risk.
Project description:Intestinal-type gastric cancer is preceded by premalignant lesions including chronic atrophic gastritis and intestinal metaplasia. In this study, we performed a scRNA-seq survey of 56,440 cells from thirteen gastric antral mucosa biopsies from nine patients with Non-atrophic gastritis (NAG), CAG, IM or early gastric cancer (EGC), and constructed a single-cell transcriptome atlas for gastric premalignant and early-malignant lesions. The thirteen biopsies, including three wild superficial gastritis (NAG) ones, three CAG ones, six IM ones and one EGC , spanned the cascade from gastritis to early gastric cancer.For each biopsy, we isolated single cells without prior selection for cell types and utilized the 10x Chromium platform to generate RNA-seq data. After removing low-quality cells (Methods), a total of 32, 332 cells that passed the quality control were retained for subsequent analysis, which yielded a median of 1941 detected genes per cell.
Project description:miRNA expression profiles in the progression of the gastric cancer According to the development of intestinal gastric cancer(GC), the normal gastric mucosa gradually evolves into gastric cancer through CSG(Chronic superficial gastritis), CAG(Chronic atrophic gastritis), IM (intestinal metaplasia) and Dys(Dysplasia). H. pylori is the main risk factor for GC, but the mechanism is still unclear. In this study, we indentified the miRNA, lncRNAs and mRNAs expression profiles in GC progression, analyzed the fuctions and pathways and investigated the relationship between non coding RNAs and H. pylori infection. Our study provided new ideas for the study of the pathogenesis of GC and a basis for the early diagnosis and treatment of GC and precancerous lesions.
Project description:To clarify the molecular pathogenesis of DFL pathogenesis using GEP. DFL shares characteristics of both NFL and MALT lymphoma. 55 total samples were examined; 10 DFL, 18 NFL, 10 gastric MALT lymphoma, 5 normal duodenal mucosa, 8 nodal reactive lymphoid hyperplasia, and 4 normal gastric mucosa.
Project description:Genome-scale DNA methylation profiling using the Infinium DNA methylation 450K BeadChip platform and samples from gastric cancer (intestinal and diffuse), precursor lesions (multifocal chronic atrophic gastritis and inestina metaplasia), non-atrophic gastritis and normal gastric mucosa.
Project description:We induced an intestinal metaplasia in human gastric mucosa in vitro, followed by the overexpression of CDX2 gene using a tet-on system.
Project description:Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) is a pan-ErbB negative regulator and intestinal stem cell marker downregulated in many malignancies. Over 91% Lrig1-CreERT2/CreERT2 (Lrig1-/-) mice developed duodenal adenomas, providing the first in vivo evidence Lrig1 acts as a tumor suppressor. We thus characterize the differential expressing transcripts in these duodenal adenomas to explore the pathegenesis. Elevated expression of the Egfr ligands was detected in adenomas compared to adjacent normal tissue. These adenomas also expressed the gastric-specific genes Gastrokine1 and Mucin5ac, indicating gastric metaplasia. In this dataset, we include the expression data obtained from proximal adenomas as well as adjacent normal tissue and wildtype proximal duodenum. These data are used to obtain 679 upregulated and 874 downregulated transcripts in tumors. Total RNA from matched duodenal tumors or adjacent normal or wildtype duodenum was isolated with Rneasy (with Dnase digestion) and used to probe the Affymetrix Mouse Gene 1.0 ST chip; the probe was prepared with Ambion Expression Target preparation Kit P/N 4411974.