Expression of gallstone disease-associated genes in non-diseased and diseased gallbladder and liver samples
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE66430 | GEO | 2016/04/21
SECONDARY ACCESSION(S): PRJNA276896
REPOSITORIES: GEO
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Project description:Gallstone disease is a major contributor to health care costs in the United States. Approximately 12 % of the U.S. population has gallstones. As a result, more than 700,000 cholecystectomies are performed in this country each year. Many of these patients are obese and have a positive family history; but surprisingly, little is known about the link between obesity, genetics and gallstone formation. Obese individuals have been shown to have supersaturated bile, larger gallbladder fasting volumes and impaired gallbladder emptying. We have recently demonstrated that leptin plays a role in gallbladder motility. In an effort to understand the genetic basis for these observations, we tested the hypothesis that leptin would alter gallbladder gene expression. Methods: Affymetrix oligonucleotide microarrays 430 2.0 were used to compare gallbladder gene expression profiles from 12 week old control saline-treated leptin-deficient (Lep ob) and from leptin-treated Lep ob female mice. Analyses were performed on pooled RNA (n=4) from the gallbladders of 12 saline-treated Lep ob mice and from 12 Lep ob mice which were administered daily IP 5 ug/g of recombinant murine leptin for 4 weeks. Resulting data were analyzed utilizing Gene Chip Operating Software or MAS 5.0. Results: Of the genes analyzed 314 were upregulated and 108 were downregulated by leptin administration. Numerous genes related to gallstone pathogenesis, gallbladder absorption/secretion, inflammatory cytokines, and insulin resistance were altered by leptin. Keywords: comparitive response to leptin
2005-12-31 | GSE3293 | GEO
Project description:Epigenome-wide methylation levels were measured in patients from Chiel with gallstone disease, gallbladder dyplasia or gallbladder cancer using Illumina Infinium methylation arrays.
2020-12-12 | E-MTAB-9868 | biostudies-arrayexpress
Project description:Gallstone disease is a worldwide common disease. However, the knowledges concerning the gallbladder in the pathogenesis of cholesterol gallstone formation remains limited. In this study, using single-cell RNA sequencing (scRNA-seq), we showed cellular heterogeneity and transcriptomic dynamics in murine gallbladder cells during the process of lithogenesis. Our results indicated gallbladder wall were subjected to remodeling during the process of lithogenesis. The major molecular events happened included proliferation of epithelial cells, infiltration of immune-cells, activation of angionesis and extracellular matrix modulation. Furthermore, we observed partial reversal of gallbladder cell transcriptomes by ursodeoxycholic acid treatment. This work thus provides novel and integral knowledges on the cellular changes during lithogenesis, which is of great significance to the understanding of pathogenesis and treatment of cholesterol gallstone.
2021-07-08 | GSE179524 | GEO
Project description:Gallstone disease is a major contributor to health care costs in the United States. Approximately 12 % of the U.S. population has gallstones. As a result, more than 700,000 cholecystectomies are performed in this country each year. Many of these patients are obese and have a positive family history; but surprisingly, little is known about the link between obesity, genetics and gallstone formation. Obese individuals have been shown to have supersaturated bile, larger gallbladder fasting volumes and impaired gallbladder emptying. We have recently demonstrated that leptin plays a role in gallbladder motility. In an effort to understand the genetic basis for these observations, we tested the hypothesis that leptin would alter gallbladder gene expression. Methods: Affymetrix oligonucleotide microarrays 430 2.0 were used to compare gallbladder gene expression profiles from 12 week old control saline-treated leptin-deficient (Lep ob) and from leptin-treated Lep ob female mice. Analyses were performed on pooled RNA (n=4) from the gallbladders of 12 saline-treated Lep ob mice and from 12 Lep ob mice which were administered daily IP 5 ug/g of recombinant murine leptin for 4 weeks. Resulting data were analyzed utilizing Gene Chip Operating Software or MAS 5.0. Results: Of the genes analyzed 314 were upregulated and 108 were downregulated by leptin administration. Numerous genes related to gallstone pathogenesis, gallbladder absorption/secretion, inflammatory cytokines, and insulin resistance were altered by leptin. Experiment Overall Design: Female B6.V-lepob obese mice (n=24) aged 7 weeks were obtained from The Jackson Laboratory (Bar Harbor, ME). Upon arrival, mice were placed on a standard chow diet and were allowed to acclimate for 1 week before starting the experiment. For leptin treatments, mice received daily intraperitoneal injections of either recombinant mouse leptin (R&D Systems, Minneapolis, MN) (n=12) at a dose of 5 µg/g body weight or with saline as a control (n=12) for 4 weeks. At 12 weeks of age, mice were fasted overnight with free access to water. The following morning the mice underwent cholecystectomy. Three gallbladders were pooled to create 4 pools in each treatment and total RNA was isolated. Affymetrix murine 430 2.0 arrays were utilized to examine altered gallbladder gene expression as a result of leptin administration. The resulting data was analyzed utlizing Gene Chip Operating Software or MAS 5.0.
2007-09-07 | E-GEOD-3293 | biostudies-arrayexpress
Project description:<p>Gallstones are crystalline deposits in the gallbladder that are traditionally classified as cholesterol, pigment or mixed stones based on their composition. Microbiota and host metabolism variances among the different types of gallstones remain largely unclear. Here, the bile and gallstone microbial species spectra of 29 subjects with gallstone disease (GSD, 24 cholesterol and 5 pigment) were revealed by type IIB restriction site-associated DNA microbiome sequencing (2bRAD-M). Among them (21 subjects: 18 cholesterol and 3 pigment), plasma samples were subjected to liquid chromatography-mass spectrometry (LC-MS) untargeted metabolomics. The microbiome yielded 896 species comprising 882 bacteria, 13 fungi, and 1 archaeon. Microbial profiling revealed significant enrichment of Cutibacterium acnes and Microbacterium sp005774735 in gallstone and Agrobacterium pusense and Enterovirga sp013044135 in the bile of cholesterol GSD subjects. The metabolome revealed 2296 metabolites, in which malvidin 3-(6''-malonylglucoside), 2-Methylpropyl glucosinolate and ergothioneine were markedly enriched in cholesterol GSD subjects. Metabolite set enrichment analysis (MSEA) demonstrated enriched bile acids biosynthesis in individuals with cholesterol GSD. Overall, the multi-omics analysis revealed that microbiota and host metabolism interaction perturbations differ depending on the disease type. Perturbed gallstone type-related microbiota may contribute to unbalanced bile acids metabolism in the gallbladder and host, representing a potential early diagnostic marker and therapeutic target for GSD.</p>
2024-03-11 | MTBLS7736 | MetaboLights
Project description:Typhoid fever, caused primarily by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening systemic disease responsible for significant morbidity and mortality worldwide. 3-5% of individuals infected with S. Typhi become chronic carriers due to bacterial persistence in the gallbladder. We have demonstrated that Salmonella forms biofilms on gallstones to establish gallbladder carriage. However, an in-depth molecular understanding of chronic carriage in the gallbladder, from the perspective of both the pathogen and host, is poorly defined. To examine the dynamics of the gallbladder in response to Salmonella infection, we performed transcriptional profiling in the mouse gallbladder at early (7 day) and chronic (21 day) time points. RNA-Seq revealed a shift from a Th1 pro-inflammatory response at 7 days post infection (DPI) towards an anti-inflammatory Th2 response by 21 DPI, characterized by increased levels of immunoglobulins and the Th2 master transcriptional regulator, GATA3. Additionally, bioinformatic analysis predicted the upstream regulation of characteristic Th2 markers including IL-4 and Stat6. Immunohistochemistry and FACS analysis confirmed a significant increase in lymphocytes, including T and B cells, at 21 DPI in mice with gallstones. Interestingly, Salmonella-specific CD4 T-cells were ten-fold higher in the gallbladder of mice with gallstones at 21 DPI. We speculate that the biofilm state allows Salmonella to resist the initial onslaught of the Th1 inflammatory response, while yet undefined events influence a switch in the host immunity towards a more permissive Type 2 response, enabling the establishment of chronic infection.
2019-09-05 | GSE136893 | GEO
Project description:Gallbladder cancer (GBC) is a lethal cancer with a poor prognosis. The lack of specific and sensitive biomarkers results in delayed diagnosis with most patients presenting at late stages of the disease. Furthermore, there is little known about the molecular mechanisms associated with GBC, especially in patients of African ancestry. This study aimed to determine dysregulated proteins in South African GBC patients to identify potential mechanisms of the disease progression and plausible biomarkers. Following ethics approval, tissues (27 GBC, 13 Gall stone disease, and 5 Normal tissues) and blood plasma (53 GBC and 73 Benign biliary pathology) were obtained from consenting patients. Protein extraction was performed on all tissues and liquid chromatography-mass spectrometry was used for proteomic profiling. A project-specific spectral library was built using the Pulsar search algorithm. Principal component and Spearman’s rank correlation analyses were performed using PAST (V4.07b). Pathway and Network analyses were conducted using REACTOME v3.7 and stringAPP (v1.7.0), respectively. Levels of the liver function tests such as total bilirubin, direct bilirubin, ALP, GGT, and AST were significantly elevated (p<0.05) in patients with GBC compared to other benign pathologies including gallstone disease. In the tissue sample comparisons, there were 63 and 199 dysregulated proteins in GBC compared to normal and gallstone, respectively. In the plasma comparison, there were 34 altered proteins in GBC compared to the benign biliary pathology group. Pathway analysis showed that the dysregulated proteins in GBC patients were enriched in pathways involved in smooth muscle contraction, metabolism, ECM organization, and integrin cell surface interactions. The identified proteins help in understanding GBC molecular mechanisms in our patient group. Furthermore, the alteration of specific proteins in both tissue and protein samples suggests their potential utility as biomarkers of GBC in this sample cohort
2023-03-11 | PXD029877 | Pride
Project description:Purpose Gallbladder cancer (GBC) is a highly malignant tumor with extremely poor prognosis. Previous studies have suggested that the carcinogenesis and progression of GBC is a multi-stage and multi-step process, but most of them focused on the genome changes. And a few studies just compared the transcriptome differences between tumor tissues and adjacent noncancerous tissues. The transcriptome changes, relating to every stage of GBC evolution, have rarely been studied. Methods We selected three cases of normal gallbladder, four cases of gallbladder with chronic inflammation induced by gallstones, five cases of early GBC, and five cases of advanced GBC, using next-generation RNA sequencing to reveal the changes in mRNAs and lncRNAs expression during the evolution of GBC. Results In-depth analysis of the sequencing data indicated that transcriptome changes from normal gallbladder to gallbladder with chronic inflammation were distinctly related to inflammation, lipid metabolism, and sex hormone metabolism; transcriptome changes from gallbladder with chronic inflammation to early GBC were distinctly related to immune activities and connection between cells; and the transcriptome changes from early GBC to advanced GBC were distinctly related to transmembrane transport of substances and migration of cells. Conclusion Expression profiles of mRNAs and lncRNAs change significantly during the evolution of GBC, in which lipid-based metabolic abnormalities play an important promotive role, inflammation and immune activities play a key role, and changes in membrane proteins are the most highlighted molecular changes.
2022-05-31 | GSE202479 | GEO
Project description:Genomic and epigenomic studies support that adenocarcinomas of the gallbladder develop according to a metaplasia-biliary intraepithelial neoplasia (BilIN)-adenocarcinoma histogenic sequence, in which metaplasia and BilIN are non-cancerous lesions of the epithelium. Moreover, recent genomic data suggest that adenocarcinoma can develop in a BilIN-dependent or -independent way, pointing toward patient-specific tumourigenic processes. Spatial transcriptomic data addressing these processes are still missing. Here, using GeoMx digital spatial profiling (NanoString), we characterized the spatial transcriptome of normal gallbladder epithelium, BilINs and adenocarcinoma coexisting within the same samples. To address intra-patient variability we profiled the whole transcriptome of a high number of regions of interest (ROIs) per sample in two patients (Patient #1, 81 year old woman: 24 ROIs; Patient #2, 53-year old man:32 ROIs), with each ROI covering approximately 200 cells of normal epithelium, low-grade BilIN, high-grade BilIN or adenocarcinoma. Our results showed that each type of lesion displayed little transcriptomic variability within the same patient, but differed significantly between patients. They also suggested that adenocarcinoma can derive from high-grade BilIN or from low-grade BilIN, with co-existing high-grade BilIN evolving via a distinct process in the latter case. We also provide strong evidence for patient-specific tumourigenic mechanisms, characterized by distinct sequences of signalling pathway activation. Among those pathways, we functionally investigated SEMAPHORIN 4A (SEMA4A) and provided evidence that repression of SEMA4A expression, as is observed in the gallbladder samples of the two patients, can enhance cell migration and survival, and perturb polarisation of the epithelial cells. In conclusion, our results support that gallbladder adenocarcinoma develops according to patient-specific processes that can be promoted by repression of SEMA4A. They underscore the need to gain gene expression data in addition to histological information to evaluate the risk of low-grade preneoplastic lesions.
2024-03-01 | GSE259311 | GEO
Project description:We determined the global microRNA expression profiles of primary human gallbladder cells and genetically reprogrammed human gallbladder cells and compared with pancreatic beta cells to ascertain the degree of cellular transdifferentatiation of insulin-producing human gallbladder cells to become beta-like cells. First, we cultured patient-derived gallbladder cells and then we transduced these with beta cell transcription factors to reprogram gallbladder cells to become beta-like cells. We used a pan-islet surface monoclonal antibody to enrich for insulin-producing reprogrammed human gallbladder cells using FACS.
2017-08-02 | E-MTAB-5554 | biostudies-arrayexpress