GENE EXPRESSION PROFILING IN PEDIATRIC APPENDICITIS
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE225466 | GEO | 2024/02/20
REPOSITORIES: GEO
Similar Datasets
Project description:Appendicitis is the most common condition necessitating emergency abdominal surgery. While most cases are localized, 20% are complicated and result in appendix perforation. The management of non-complicated appendicitis varies across different medical centers, encompassing both surgical and non-surgical options, whereas complicated appendicitis is predominantly managed surgically. Differentiating them poses a clinical challenge, especially in pediatric patients, crucial for guiding appropriate treatment strategies. Therefore, there is an unmet need for biomarkers to distinguish the two entities. Here we examined the utility of epigenetic liquid biopsies in appendicitis. We used DNA methylation markers specific to immune and gastrointestinal epithelial cells to assess the tissue origins of plasma cell-free DNA (cfDNA) in patients with appendicitis. Appendix epithelium cfDNA was not detected in plasma samples from children with appendicitis relative to patients with abdominal pain and controls. In contrast, neutrophil and regulatory T-cell cfDNA were elevated in appendicitis enhancing the specificity and sensitivity of appendicitis diagnosis beyond the information provided by neutrophil counts. Notably, eosinophil cfDNA was most significantly elevated in children with perforated compared with non-perforated appendicitis. This finding was cross-validated using a machine-learning approach. In conclusion, eosinophil cfDNA can serve as a non-invasive biomarker for diagnosing perforated appendicitis.
2025-04-30 | GSE275452 | GEO
Project description:Background: The diagnosis of acute appendicitis can be surprisingly difficult without computed tomography, which carries significant radiation exposure. Genome-wide expression profiling was applied to whole blood RNA of acute appendicitis patients versus patients with other abdominal disorders, in order to identify biomarkers of appendicitis. From a large cohort of emergency patients, a discovery set of patients with surgically confirmed appendicitis, or abdominal pain from other causes, was identified. RNA from whole blood was profiled by microarrays, and RNA levels were filtered by a combined fold-change (>2) and p value (<0.05). A separate set of patients, including patients with respiratory infections, was used to validate a partial least squares discriminant (PLSD) prediction model. Results: Transcript profiling identified 37 differentially expressed genes (DEG) in appendicitis versus abdominal pain patients. The DEG list contained 3 major ontologies: infection-related, inflammation-related, and ribosomal processing. Appendicitis patients had lower level of neutrophil defensin mRNA (DEFA1,3), but higher levels of alkaline phosphatase (ALPL) and interleukin-8 receptor-ß (IL8RB), which was confirmed in a larger cohort of 60 patients using droplet digital PCR (ddPCR). Conclusions: Patients with acute appendicitis have detectable changes in the mRNA expression levels of factors related to neutrophil inate defense systems. The low defensin mRNA levels suggest that appendicitis patient's immune cells are not directly activated by pathogens, but are primed by diffusible factors in the microenvironment of the infection. The detected biomarkers are consistent with prior evidence that biofilm-forming bacteria in the appendix may be an important factor in appendicitis.
2016-06-08 | GSE83091 | GEO
Project description:GENE EXPRESSION PROFILING IN PEDIATRIC APPENDICITIS
| PRJNA935751 | ENA
Project description:We used the Illumina Infinium HumanMethylation EPIC beadchip array to profile 31 pediatric tumors with the histological diagnosis of anaplastic pilocytic astrocyoma (PA). PA with anaplasia has been defined in the 2016 WHO classification as a tumor with PA morphology and >4 mitoses per 10 HPF, with or without necrosis with a potential worse outcome. DNA Methylation based studies performed mainly in adults have put forward this subtype as a distinct entity. After performing the same techniques on pediatric samples, our findings argue that the diagnostic histomolecular criteria established for anaplasia in adult PA are not of diagnostic or prognostic value in a pediatric setting.
2019-11-08 | E-MTAB-8390 | biostudies-arrayexpress
Project description:Gene expression was evaluated in 9 appendix samples removed from patients who went to the operating room with the diagnosis of acute appendicitis and 4 samples removed for non-inflammatory reasons. A circumferential piece of tissue was obtained at the distal aspect of each specimen. The tissue was flash frozen at -80 degrees for later processing. Frozen specimens were homogenized into TriReagent and RNA was isolated according to the manufacturerâs instruction. RNA was processed and hybridized to Affymetrix microarray. Experiment Overall Design: 9 patients and 4 controls
2008-06-16 | E-GEOD-9579 | biostudies-arrayexpress
Project description:Gene expression was evaluated in 9 appendix samples removed from patients who went to the operating room with the diagnosis of acute appendicitis and 4 samples removed for non-inflammatory reasons. A circumferential piece of tissue was obtained at the distal aspect of each specimen. The tissue was flash frozen at -80 degrees for later processing. Frozen specimens were homogenized into TriReagent and RNA was isolated according to the manufacturer's instruction. RNA was processed and hybridized to Affymetrix microarray. Keywords: Disease state analysis
2008-04-22 | GSE9579 | GEO
Project description:ImportanceAppendicitis is the most common indication for urgent surgery in the pediatric population, presenting across a range of severity and with variable complications. Differentiating simple appendicitis (SA) and perforated appendicitis (PA) on presentation may help direct further diagnostic workup and appropriate therapy selection, including antibiotic choice and timing of surgery.ObjectiveTo provide a mechanistic understanding of the differences in disease severity of appendicitis with the objective of developing improved diagnostics and treatments, specifically for the pediatric population.Design, setting, and participantsThe Gene Expression Profiling of Pediatric Appendicitis (GEPPA) study was a single-center prospective exploratory diagnostic study with transcriptomic profiling of peripheral blood collected from a cohort of children aged 5 to 17 years with abdominal pain and suspected appendicitis between November 2016 and April 2017 at the Alberta Children's Hospital in Calgary, Alberta, Canada, with data analysis reported in August 2023. There was no patient follow-up in this study.ExposureSA, PA, or nonappendicitis abdominal pain.Main outcomes and measuresBlood transcriptomics was used to develop a hypothesis of underlying mechanistic differences between SA and PA to build mechanistic hypotheses and blood-based diagnostics.ResultsSeventy-one children (mean [SD] age, 11.8 [3.0] years; 48 [67.6%] male) presenting to the emergency department with abdominal pain and suspected appendicitis were investigated using whole-blood transcriptomics. A central role for immune system pathways was revealed in PA, including a dampening of major innate interferon responses. Gene expression changes in patients with PA were consistent with downregulation of immune response and inflammation pathways and shared similarities with gene expression signatures derived from patients with sepsis, including the most severe sepsis endotypes. Despite the challenges in identifying early biomarkers of severe appendicitis, a 4-gene signature that was predictive of PA compared to SA, with an accuracy of 85.7% (95% CI, 72.8-94.1) was identified.ConclusionsThis study found that PA was complicated by a dysregulated immune response. This finding should inform improved diagnostics of severity, early management strategies, and prevention of further postsurgical complications.
| S-EPMC10877506 | biostudies-literature
Project description:BACKGROUND: Appendicitis followed by appendectomy (AA) at a young age protects against later inflammatory bowel disease (IBD). Using a novel murine appendicitis model we earlier demonstrated that AA proffered significant protection against subsequent experimental colitis. AIM: To delineate genes and biological pathways involved in the protective effect of AA against subsequent colitis using gene set enrichment analysis (GSEA) of DNA microarray data. METHODS: Appendicitis and appendicectomy was done (5 week old male BALB/c mice) near the most proximal colon (caecal lymphoid follicles) and colonic samples were harvested from the most distal colon. Two consecutive laparotomies were done in control Sham-Sham (SS) mice. RNA was extracted (TRIzol®) from 4 individual colonic samples per group (AA group vs. SS group) with each sample taken independently through Affymetrix® microarray hybridization. For GSEA, data for more than 23,000 genes were exported from Partek and analyzed with GSEA software (with 2852 gene sets encoded) to establish correlates with phenotypes of the gene sets. RESULTS: Distal colonic expression of 636 gene-sets were significantly upregulated in AA group samples (False Discovery Rates (FDR) values < 1 % and p value < 0.001; stringent statistical selection). These were validated by quantitative PCR of 14 selected genes across the immunological spectrum and over time-intervals of 3 days, 14 days and 28 days. CONCLUSIONS: Many key immunological, apoptosis-related and cellular function-associated gene-sets involved in the protective effect of AA in experimental colitis were identified. Further analysis of these profiles and biological pathways will assist utilizing these gene products and manipulating various aspects of these pathways to develop better therapeutic strategies in the management of intractable IBD. Appendicitis and appendicectomy was done (5 week old male BALB/c mice) near the most proximal colon (caecal lymphoid follicles) and colonic samples were harvested from the most distal colon. Two consecutive laparotomies were done in control Sham-Sham (SS) mice. RNA was extracted (TRIzol®) from 4 individual colonic samples per group (AA group vs. SS group) with each sample taken independently through Affymetrix® microarray hybridization. variable_protocol: appendicitis and appendectomy: AA1, AA2, AA3, AA4 variable_protocol: sham/sham surgery: SS1, SS2, SS3, SS4 repeat_biological replicate: AA1, AA2, AA3, AA4 repeat_biological replicate: SS1, SS2, SS3, SS4 Upregulated gene-set linked as supplementary file.
2010-09-01 | E-GEOD-23914 | biostudies-arrayexpress
Project description:Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a good prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. Potential biomarkers for PA patients, especially the non-BRAF-mutated ones are needed. Cerebrospinal fluid (CSF) is a valuable source of brain tumor biomarkers. Extracellular vesicles express valuable disease targets. These can be isolated from CSF from waste extraventricular drainage (EVD). We analyzed the proteome of EVD CSF from 24 PA, cerebral hemorrhage (CH, non-tumor controls), or medulloblastoma (MB, unrelated tumoral controls) patients. 3072 proteins were identified, 47.1%, 65.6%, and 86.2% of which expressed in the unprocessed total, and its microvesicle (Mv), and exosome (Ex) fractions. Bioinformatics identified 50 statistically significant proteins in the comparison between PA and HC, and PA and MB patients, in the same fractions. Kinase enrichment analysis predicted five enriched kinases involved in signaling. Among these, only Cyclin-dependent kinase 2 (CDK2) kinase was overexpressed in PA samples. PLS-DA highlighted inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western Blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers to discriminate among pilocytic astrocytoma, and unrelated tumoral (MB) or non-tumoral conditions, in all the fractions examined, proposed to be prospectively validated in the plasma for translational medicine applications.
2024-05-23 | PXD050589 | Pride