Gene expression profiling of nasal polyps associated with chronic sinusitis and aspirin-sensitive asthma

Konstantina M Stankovic, Hernan Goldsztein, Douglas D Reh, Michael P Platt, Ralph Metson
Laryngoscope 2008, 118 (5): 881-9

OBJECTIVE: To identify genes whose expression is most characteristic of chronic rhinosinusitis and aspirin-sensitive asthma through genome-wide transcriptional profiling of nasal polyp tissue.

STUDY DESIGN: Prospective, controlled study conducted at a tertiary care institution.

METHODS: Thirty genome-wide expression microarrays were used to compare nasal polyp tissue from patients with chronic rhinosinusitis alone (CRS, n = 10) or chronic rhinosinusitis and a history of aspirin-sensitive asthma (ASA, n = 10) to normal sinonasal mucosa from patients who underwent surgery for non-sinus related conditions (controls, n = 10). Genes found to be most characteristic of each polyp phenotype, as determined from bioinformatic analyses, were validated using real-time quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry in different patient sets.

RESULTS: The transcriptional signature of the control mucosa was distinctly different from that of either polyp phenotype. Genes most characteristic of the CRS phenotype included two upregulated genes--met proto-oncogene (MET) and protein phosphatase 1 regulatory subunit 9B (PPP1R9B)-and two downregulated genes--prolactin-induced protein (PIP) and zinc alpha2-glycoprotein (AZGP1). The gene most characteristic of the ASA phenotype was periostin (POSTN), which was upregulated relative to controls. Differences between the CRS and ASA phenotypes were associated with alterations in the 6p22, 22q13, and 1q23 chromosomal regions.

CONCLUSIONS: Nasal polyps appear to have characteristic transcriptional signatures compared to normal sinonasal mucosa. The five genes identified in this study likely play roles in the pathogenesis of polyps associated with CRS and ASA, and are therefore attractive targets for novel medical therapies for these common debilitating diseases.

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