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: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: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:Helicobacter pylori colonization of the human stomach is a strong risk factor for gastric cancer. To investigate H. pylori-induced gastric molecular alterations, we used a Mongolian gerbil model of gastric carcinogenesis. Histologic evaluation revealed varying levels of atrophic gastritis (a premalignant condition characterized by parietal and chief cell loss) in H. pylori-infected animals, and transcriptional profiling revealed a loss of markers for these cell types. We then assessed the spatial distribution and relative abundance of proteins in the gastric tissues using imaging mass spectrometry and liquid chromatography with tandem mass spectrometry (LC-MS/MS). We detected striking differences in protein content of corpus and antrum tissues. 492 proteins were preferentially localized to the corpus in uninfected animals. The abundance of 91 of these proteins was reduced in H. pylori-infected corpus tissues exhibiting atrophic gastritis compared to infected corpus tissues with non-atrophic gastritis or uninfected corpus tissues; these included numerous proteins with metabolic functions. Fifty proteins localized to the corpus in uninfected animals were diffusely delocalized throughout the stomach in infected tissues with atrophic gastritis; these included numerous proteins with roles in protein processing. Corresponding alterations were not detected in animals infected with a H. pylori ∆cagT mutant (lacking Cag type IV secretion system activity). These results indicate that H. pylori can cause loss of proteins normally localized to the gastric corpus as well as diffuse delocalization of corpus-specific proteins, resulting in marked changes in the normal gastric molecular partitioning into distinct corpus and antrum regions.
Project description:Aberrant DNA methylation is implicated in the epigenetic field defect seen in gastric cancer (GC). Our aim in this study was to identify predictive biomarkers by screening for DNA methylation in noncancerous background gastric mucosa from GC patients. A total of 46 endoscopically obtained human gastric mucosa, 10 gastric cancer and 5 cell lines were analyzed using MCA microarray. Aberrant DNA methylation was compared with clinicopathological features. Healthy individuals were divided into two groups based on the types of chronic gastritis; A: antrum-predominant gastritis P or C: pangastritis or corpus-predominant gastritis
Project description:Gastric cancer is an important health problem because it is difficult to diagnose and treat in advanced stage. This makes that the prognosis of gastric cancer patients remains scarce. Currently it is known that the cause of gastric cancer is attributed to chronic infection with Helicobacter pylori. Its persistent infection leads to development of chronic atrophic gastritis that is considered as a predecessor stage of intestinal-type gastric cancer. The understanding of the alteration of molecular mechanisms during the early stages of the development of gastric cancer, and the identification of their potential biomarkers can allow a rapid diagnosis that leads to an improvement diagnosis and increase the patient’s prognosis. We analyzed gene expression profiles of patients with chronic atrophic gastritis and gastric cancer through microarray analysis, functional enrichment analysis and validation of gene expression by quantitative PCR. Gene expression profiles in patients with chronic atrophic gastritis showed molecular changes of the gastric mucosa, which leads to intestinal metaplasia and subsequently, gastric cancer. In gastric cancer the gene expression profile showed the stage of tumor progression, the product of these genes are potential biomarkers of early stages of cancer that can be potential therapeutic targets. Accordingly, the transcriptome analysis revealed several gene groups are related to development of chronic atrophic gastritis, some of which were inhibited in gastric cancer patients. The increased expression of CLDN1, CLDN7, OLFM4, c-Myc and MMP-9 genes in chronic atrophic gastritis and gastric cancer point outs to their use as promising biomarkers for the early diagnosis of gastric cancer.
Project description:In this study, we aimed to reveal whether gastric mucosa with AIG has a specific gene expression profile, involving in its histology and chronic inflammation. To approach this, we performed comprehensive analysis of gene expression using gastric mucosa with atuoimmune gastritis, that with H. pylori-associated gastritis and healthy mucosa without any inflammation. Potential mechanisms of the gene expression changes in gastric mucosa with AIG were also explored.
Project description:Background & Aims: The association between chronic inflammation and gastric carcinogenesis is well established, but it is not clear how immune cells and cytokines regulate this process. We investigated the role of interleukin 27 (IL27) in the development of gastric atrophy, hyperplasia, and metaplasia (preneoplastic lesions associated with inflammation-induced gastric cancer) in mice with autoimmune gastritis. Methods: We performed studies with TxA23 mice (control mice), which express a T-cell receptor against the H+/K+ adenosine triphosphatase α chain and develop autoimmune gastritis, and TxA23xEbi3-/- mice, which develop gastritis but do not express IL27. In some experiments, mice were given high-dose tamoxifen to induce parietal cell atrophy and spasmolytic polypeptide-expressing metaplasia (SPEM). Recombinant IL27 was administered to mice with mini osmotic pumps. Stomachs were collected and analyzed by histopathology and immunofluorescence; we used flow cytometry to measure IL27 and identify immune cells that secrete IL27 in the gastric mucosa. Single-cell RNA sequencing was performed on immune cells that infiltrated stomach tissues. Results: We identified IL27-secreting macrophages and dendritic cell in the corpus of mice with chronic gastritis (TxA23 mice). Mice deficient in IL27 developed more severe gastritis, atrophy, and SPEM than control mice. Administration of recombinant IL27 significantly reduced the severity of inflammation, atrophy, and SPEM in mice with gastritis. Single-cell RNA sequencing showed that IL27 acted almost exclusively on stomach-infiltrating CD4+ T cells to suppress expression of inflammatory genes. Conclusions: In studies of mice with autoimmune gastritis, we found that IL27 is an inhibitor of gastritis and SPEM, suppressing CD4+ T-cell–mediated inflammation in the gastric mucosa.