Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.
Int Forum Allergy Rhinol. 2018 May;8(5):592-604. doi: 10.1002/alr.22083. Epub 2018 Jan 16.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is known to have 2 phenotypes in East Asia. Eosinophilic CRSwNP (ECRSwNP), defined as tissue eosinophilia and easily recurrent, is distinguished from other non-eosinophilic CRSwNP (NECRSwNP) types. However, the pathogenesis of each remains unclear.
Nasal polyp tissues from ECRS (ECRSwNP) and NECRS (NECRSwNP) patients were obtained, and their comprehensive gene expression profiles were investigated by microarray analysis. Bioinformatics approaches (eg, Ingenuity Pathway Analysis [IPA]) were used to interrogate the data sets.
Hierarchical clustering and principal component analysis (PCA) collectively showed that ECRSwNP and NECRSwNP had distinct gene expression patterns. Of note, these genes could be divided into 8 distinctive clusters having different expression patterns and functions. Upstream Regulator Analysis revealed that not only T-helper 2 (Th2) and the eosinophilia-related molecules (interleukin 4 [IL4], IL5, and colony stimulating factor 2 [CSF2]) reported so far, but also cell cycle regulators (cyclin dependent kinase inhibitor 1A [CDKNA1] and cyclin D1 [CCND1]) and a tissue fibrosis-related molecule (transforming growth factor β [TGFβ]) were identified in ECRSwNP. On the other hand, mainly interferons (IFNs) and acute inflammatory cytokines (IL1 and IL6) were predicted as upstream regulators in NECRSwNP.
These results are useful for understanding the molecular basis of the mechanisms of CRSwNP and point to new targets for developing specific biomarkers and personalized therapeutic strategies for CRSwNP.
已知东亚地区慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）存在 2 种表型。嗜酸性粒细胞性 CRSwNP（ECRSwNP）定义为组织嗜酸性粒细胞增多且易于复发，与其他非嗜酸性粒细胞性 CRSwNP（NECRSwNP）类型不同。然而，每种疾病的发病机制仍不清楚。
从 ECRS（ECRSwNP）和 NECRS（NECRSwNP）患者的鼻息肉组织中获取，并通过微阵列分析研究其综合基因表达谱。采用生物信息学方法（如Ingenuity Pathway Analysis [IPA]）来分析数据集。
层次聚类和主成分分析（PCA）共同表明，ECRSwNP 和 NECRSwNP 具有明显不同的基因表达模式。值得注意的是，这些基因可以分为 8 个不同的簇，具有不同的表达模式和功能。上游调控因子分析显示，不仅到目前为止报道的 Th2 和嗜酸性粒细胞相关分子（白细胞介素 4 [IL4]、白细胞介素 5 [IL5]和集落刺激因子 2 [CSF2]），而且细胞周期调节剂（细胞周期蛋白依赖性激酶抑制剂 1A [CDKNA1]和细胞周期蛋白 D1 [CCND1]）和组织纤维化相关分子（转化生长因子β [TGFβ]）也被鉴定为 ECRSwNP 的上游调控因子。另一方面，主要干扰素（IFNs）和急性炎症细胞因子（IL1 和 IL6）被预测为 NECRSwNP 的上游调控因子。
这些结果有助于了解 CRSwNP 机制的分子基础，并为开发针对 CRSwNP 的特异性生物标志物和个体化治疗策略提供新的靶点。
