Meta-analysis of global and high throughput public gene array data for robust vascular gene expression discovery in chronic rhinosinusitis: Implications in controlled release

J Control Release. 2021 Feb 10:330:878-888. doi: 10.1016/j.jconrel.2020.10.061. Epub 2020 Nov 2.

Abstract

Background: Chronic inflammation is known to cause alterations in vascular homeostasis that directly affects blood vessel morphogenesis, angiogenesis, and tissue permeability. These phenomena have been investigated and exploited for targeted drug delivery applications in the context of cancers and other disease processes. Vascular pathophysiology and its associated genes and signaling pathways, however, have not been systematically investigated in patients with chronic rhinosinusitis (CRS). Understanding the interplay between key vascular signaling pathways and top biomarkers associated with CRS may facilitate the development of new targeted delivery strategies and treatment paradigms. Herein, we report findings from a gene meta-analysis to identify key vascular pathways and top genes involved in CRS.

Methods: Proprietary software (Illumina BaseSpace Correlation Engine) and open-access data sets were used to perform a gene meta-analysis to systematically determine significant differences between key vascular biomarkers and vascular signaling pathways expressed in sinonasal tissue biopsies of controls and patients with CRS.

Results: Thirteen studies were initially identified, and then reduced to five after applying exclusion principle algorithms. Genes associated with vasculature development and blood vessel morphogenesis signaling pathways were identified to be overexpressed among the top 15 signaling pathways. Out of many significantly upregulated genes, the levels of pro angiogenic genes such as early growth response (EGR3), platelet endothelial cell adhesion molecule (PECAM1) and L-selectin (SELL) were particularly significant in patients with CRS compared to controls.

Discussion: Key vascular biomarkers and signaling pathways were significantly overexpressed in patients with CRS compared to controls, suggesting a contribution of vascular dysfunction in CRS pathophysiology. Vascular dysregulation and permeability may afford opportunities to develop drug delivery systems to improve efficacy and reduce toxicity of CRS treatment.

Keywords: Chronic rhinosinusitis; Drug delivery; Meta-analysis; Neoangiogenesis; Signaling pathways; Vascular permeability.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chronic Disease
  • Delayed-Action Preparations / therapeutic use
  • Gene Expression
  • Humans
  • Rhinitis* / drug therapy
  • Rhinitis* / genetics
  • Sinusitis* / drug therapy
  • Sinusitis* / genetics

Substances

  • Delayed-Action Preparations