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


METHODS
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.
Stankovic
Konstantina M
KM
Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
Goldsztein
Hernan
H
Reh
Douglas D
DD
Platt
Michael P
MP
Metson
Ralph
R
D054392:Adipokines; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D002908:Chronic Disease; D015536:Down-Regulation; D004342:Drug Hypersensitivity / Q000453:epidemiology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009298:Nasal Polyps / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D040081:Protein Array Analysis; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012852:Sinusitis / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D000090203:Zn-Alpha-2-Glycoprotein
D054392:Adipokines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin; D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein; C000715470:MAS1 protein, human; C488892:PIP protein, human