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Acute appendicitis: transcript profiling of blood identifies promising biomarkers and potential underlying processes

Authors
  • Chawla, Lakhmir S.1, 2
  • Toma, Ian3
  • Davison, Danielle1
  • Vaziri, Khashayar4
  • Lee, Juliet1, 4
  • Lucas, Raymond5
  • Seneff, Michael G.5
  • Nyhan, Aoibhinn3
  • McCaffrey, Timothy A.3, 6
  • 1 The George Washington University Medical Center, Department of Anesthesiology and Critical Care Medicine, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA , Washington, DC (United States)
  • 2 The George Washington University Medical Center, The Department of Medicine, Veterans Affairs Medical Center, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA , Washington, DC (United States)
  • 3 The George Washington University Medical Center, Department of Medicine, Division of Genomic Medicine, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA , Washington, DC (United States)
  • 4 The George Washington University Medical Center, Department of Surgery, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA , Washington, DC (United States)
  • 5 The George Washington University Medical School and GW Medical Faculty Associates, Department of Emergency Medicine, Washington, DC, USA , Washington, DC (United States)
  • 6 The George Washington University Medical Center, Department of Microbiology, Immunology, and Tropical Medicine, 2300 I Street, NW Ross 443, Washington, DC, 20037, USA , Washington, DC (United States)
Type
Published Article
Journal
BMC Medical Genomics
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jul 15, 2016
Volume
9
Issue
1
Identifiers
DOI: 10.1186/s12920-016-0200-y
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundThe diagnosis of acute appendicitis can be surprisingly difficult without computed tomography, which carries significant radiation exposure. Circulating blood cells may carry informative changes in their RNA expression profile that would signal internal infection or inflammation of the appendix.MethodsGenome-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.ResultsTranscript 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 (CXCR2/IL8RB), which was confirmed in a larger cohort of 60 patients using droplet digital PCR (ddPCR).ConclusionsPatients with acute appendicitis have detectable changes in the mRNA expression levels of factors related to neutrophil innate 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.

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