Gene expression profiles in human nasal polyp tissues studied by means of DNA microarray.
BACKGROUND
Nasal polyposis (NP) is a chronic inflammatory disease of the sinuses. Its pathogenesis is unknown. DNA microarray analysis allows simultaneous measurement of expression of thousands of genes in the same tissue sample and might help to identify gene alterations in various disorders.


OBJECTIVE
We sought to screen for disease-related genes in NP by using DNA microarrays and to validate the altered expression of selected genes at the mRNA and protein level.


METHODS
Expression microarrays containing approximately 10,500 genes were used to compare individual gene profiles of NP samples (n=10) and normal mucosal samples obtained from sphenoid sinuses in patients undergoing pituitary surgery (n=4). Four of the 5 most upregulated, and the single most downregulated, genes were retested by means of quantitative RT-PCR and immunohistochemistry in a different set of NP and normal mucosal samples obtained from the ethmoid and sphenoid sinuses.


RESULTS
Compared with normal sinus tissue, 192 genes were upregulated at least 2-fold, and 156 genes were downregulated by at least 50% in NP samples (approximately 3% of genes evaluated). Four of the top 5 overexpressed genes (statherin, 48.0-fold; prolactin-induced protein [PIP] , 24.9-fold; lactoferrin, 26.6-fold; and deleted in malignant brain tumor 1 [DMBT1] , 30.3-fold) and the most underexpressed gene (Clara cell 10-kd protein [CC10] , -20.1-fold) were selected and retested by means of quantitative RT-PCR and immunohistochemical staining. Quantitative RT-PCR and immunohistochemical staining confirmed the differential expression of all except statherin in NP tissue.


CONCLUSIONS
DNA microarrays can provide new insight into the possible pathophysiologic processes involved in NP.
Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21224-6821, USA.
Zheng
Z
Liu
Jean
J
Kim
Joseph P
JP
Sypek
I-Ming
IM
Wang
Heidi
H
Horton
Frank G
FG
Oppenheim
Bruce S
BS
Bochner
D000328:Adult; D000368:Aged; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*