Department of Otolaryngology-Head and Neck Surgery, Boston University, Boston, Massachusetts 02118, USA.
Otolaryngol Head Neck Surg. 2011 May;144(5):802-8. doi: 10.1177/0194599810395091.
To perform a comprehensive molecular pathways analysis of genes identified through genome-wide expression profiling and the published literature for chronic sinusitis with polyps.
Molecular pathways analysis.
Academic medical center.
A molecular pathways analysis of gene biomarkers discovered through hypothesis-driven and high-throughput molecular studies was performed. Genes identified with a PubMed literature search were analyzed with Ingenuity Pathways Analysis software to identify central molecules implicated in the pathogenesis of chronic sinusitis with polyps. The central pathways were then compared with those identified through genome-wide expression profiling of ethmoid polyps.
A total of 97 molecules were investigated with Ingenuity Pathways Analysis based on 55 studies that evaluated differences in gene expression (39), genetic variation (12), or proteomics (4). The analysis revealed 9 statistically significant molecular networks containing central nodes that included transcription factors, protein kinases, cytokines, and growth factors/receptors. The highest scoring networks implicated nuclear factor kappa-B, tumor necrosis factor, and mitogen-activated protein kinases. The majority of pathways in the literature review analysis overlapped with those identified through a single genome-wide expression study.
Chronic sinusitis with polyps is a complex disease with suspected contribution of multiple genetic and environmental factors. The search for causative genes has led to the discovery of numerous candidates. Pathways analysis applied to these candidate genes identified common central molecules that are likely to be key mediators of the disease process. Novel therapies targeting these molecules may be applicable for the treatment of chronic sinusitis with polyps.
对通过全基因组表达谱分析和已发表文献鉴定的慢性鼻息肉鼻窦炎相关基因进行全面的分子通路分析。
分子通路分析。
学术医疗中心。
对通过假设驱动和高通量分子研究发现的基因生物标志物进行分子通路分析。通过 PubMed 文献检索鉴定的基因，使用 Ingenuity Pathways Analysis 软件进行分析，以确定与慢性鼻息肉鼻窦炎发病机制相关的关键分子。然后将这些关键通路与通过筛窦息肉的全基因组表达谱鉴定的通路进行比较。
基于 55 项研究，共对 97 个分子进行了 Ingenuity Pathways Analysis 分析，这些研究评估了基因表达（39 项）、遗传变异（12 项）或蛋白质组学（4 项）的差异。分析揭示了 9 个具有统计学意义的分子网络，包含转录因子、蛋白激酶、细胞因子和生长因子/受体等核心节点。评分最高的网络涉及核因子 kappa-B、肿瘤坏死因子和丝裂原激活蛋白激酶。文献综述分析中的大多数通路与单一全基因组表达研究中鉴定的通路重叠。
慢性鼻息肉鼻窦炎是一种复杂的疾病，可能涉及多种遗传和环境因素。对致病基因的研究已经发现了许多候选基因。对这些候选基因进行通路分析，确定了常见的核心分子，这些分子可能是疾病过程的关键介质。针对这些分子的新型治疗方法可能适用于慢性鼻息肉鼻窦炎的治疗。
