Vijay K Anand1, Ashutosh Kacker, Andres F Orjuela, Clark Huang, Casey Manarey, Jenny Xiang. 1. Department of Otorhinolaryngology-Head and Neck Surgery, Rhinology Laboratory, The New York Presbyterian Hospital-Weill Cornell Campus, Weill Medical College of Cornell University, New York, NY 10021, USA. vijayanandmd@aol.com
Abstract
BACKGROUND: The main objective in this preliminary experiment was to compare gene expression in the sinus mucosa of patients with chronic hyperplastic rhinosinusitis (CRS) against normal subjects, using gene microarray technology. The specific aim was to examine alterations in inflammatory mediator expression in patients with CRS. We performed a prospective experimental study. METHODS: Total RNA samples were obtained from the sinus mucosa biopsies of 14 patients with chronic hyperplastic sinusitis and 4 normal controls, using the Affymetrix recommended protocol. The data for 22,000 genes on the GeneChip U133A were generated from 18 hybridizations. Affymetrix GeneChip 5.0 was used as the image acquisition software for the U133A chips. Data normalization, log transformation, statistical analysis, and pattern study were performed with GeneSpring software. Comparison between patients with CRS and normal controls were performed using the Welch t-test, with log transformed data. RESULTS: There were a total of 1283 genes scored as differentially expressed between groups. The value of p, the probability of a false positive, was set to <0.05. Hierarchical clustering was applied to study coexpression patterns of the 1283 significant genes. The inflammatory pathway was overlaid with the differential expressed gene list. Four genes involved in the inflammatory pathway, interleukin (IL)-6, IL-12A, IL-13, and tumor necrosis factor (TNF) alpha (2) were consistently overexpressed in patients with hyperplastic CRS. CONCLUSION: There is overexpression of four major genes of the inflammatory pathway (IL-6, IL-12A, IL-13, and TNF-alpha (2)) in patients with CRS compared with the normal population. Defining gene expression profiles may help elucidate new key factors in the pathogenesis of CRS and perhaps aid in the development of new therapeutic modalities.
BACKGROUND: The main objective in this preliminary experiment was to compare gene expression in the sinus mucosa of patients with chronic hyperplastic rhinosinusitis (CRS) against normal subjects, using gene microarray technology. The specific aim was to examine alterations in inflammatory mediator expression in patients with CRS. We performed a prospective experimental study. METHODS: Total RNA samples were obtained from the sinus mucosa biopsies of 14 patients with chronic hyperplastic sinusitis and 4 normal controls, using the Affymetrix recommended protocol. The data for 22,000 genes on the GeneChip U133A were generated from 18 hybridizations. Affymetrix GeneChip 5.0 was used as the image acquisition software for the U133A chips. Data normalization, log transformation, statistical analysis, and pattern study were performed with GeneSpring software. Comparison between patients with CRS and normal controls were performed using the Welch t-test, with log transformed data. RESULTS: There were a total of 1283 genes scored as differentially expressed between groups. The value of p, the probability of a false positive, was set to <0.05. Hierarchical clustering was applied to study coexpression patterns of the 1283 significant genes. The inflammatory pathway was overlaid with the differential expressed gene list. Four genes involved in the inflammatory pathway, interleukin (IL)-6, IL-12A, IL-13, and tumor necrosis factor (TNF) alpha (2) were consistently overexpressed in patients with hyperplastic CRS. CONCLUSION: There is overexpression of four major genes of the inflammatory pathway (IL-6, IL-12A, IL-13, and TNF-alpha (2)) in patients with CRS compared with the normal population. Defining gene expression profiles may help elucidate new key factors in the pathogenesis of CRS and perhaps aid in the development of new therapeutic modalities.
Authors: Spencer C Payne; Joseph K Han; Phillip Huyett; Julie Negri; Elizabeth Z Kropf; Larry Borish; John W Steinke Journal: Am J Rhinol Date: 2008 Nov-Dec