Distinct type 2-high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma
Distinct type 2-high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma
复制标题
慢性鼻窦炎伴鼻息肉并伴有哮喘的独特 2 型高炎症相关分子特征
DOI：
10.1186/s13601-020-00332-z
复制
发表时间：
2020-07-03
影响因子：
4.4
通讯作者：
Wang，Chengshuo
中科院分区：
文献类型：
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作者：
Wang，Ming;Bu，Xiangting;Wang，Chengshuo
背景慢性鼻窦炎伴鼻息肉（CRSwNP）并合并哮喘的患者病情更为严重且难以治疗。然而，与 CRSwNP 合并哮喘 (CRSwNP + AS) 相关的分子内型尚不清楚。本研究旨在探讨2型炎症的特征以及与CRSwNP + AS相关的分子特征。方法共有195名受试者；包括 65 名 CRSwNP + AS 患者、99 名单独使用 CRSwNP 的患者和 31 名健康对照受试者；参加了该研究。对 CRSwNP + AS 患者、单独 CRSwNP 患者和对照受试者的鼻组织进行炎症细胞浸润和总 IgE 浓度的评估。进行全转录组测序，并分析差异表达 (DE) mRNA 和长非编码 RNA (lncRNA) 及其相关通路。评估了 2 型细胞因子与局部嗜酸性粒细胞、组织 IgE 和转录组特征之间的相关性。结果发现，与单独 CRSwNP 患者的鼻组织相比，CRSwNP + AS 患者的鼻组织中局部嗜酸性粒细胞浸润和总 IgE 水平显着更高。此外，CRSwNP + AS 患者的特应性和复发率明显高于单独 CRSwNP 患者（分别为 62.5% vs 28.6% 和 66.7% vs 26.9%）。 RNA 测序分析确定了 CRSwNP + AS 与对照以及单独 CRSwNP 与对照共有的 1988 个常见 DE-mRNA 和 176 个常见 DE-lncRNA。加权基因共表达网络分析 (WGCNA) 确定 LINC01146 是 CRSwNP 两种亚型中失调的枢纽 lncRNA。总体而言，在 CRSwNP + AS 和单独的 CRSwNP 之间鉴定出 968 个 DE-mRNA 和 312 个 DE-lncRNA。通路富集分析和WGCNA均表明CRSwNP + AS的表型特征主要与花生四烯酸代谢、2型细胞因子相关通路和纤溶通路活性较高以及IL-17信号通路活性较低有关。此外，2型细胞因子的表达； IL5和IL13与局部嗜酸性粒细胞浸润、组织IgE水平以及与花生四烯酸代谢相关的DE-mRNA表达呈正相关。此外，WGCNA 将 HK3-006 鉴定为黄色模块中的枢纽 lncRNA，与 CRSwNP + AS 的表型特征最为正相关。结论与单独患有 CRSwNP + AS 的患者相比，患有 CRSwNP + AS 的患者在鼻组织中具有独特的 2 型高炎症相关分子特征。
BackgroundPatients with chronic rhinosinusitis with nasal polyps (CRSwNP) and comorbid asthma have more severe disease and are difficult to treat. However, the molecular endotypes associated with CRSwNP with comorbid asthma (CRSwNP + AS) are not clear. This study aimed to investigate the characteristics of type 2 inflammation and the molecular signatures associated with CRSwNP + AS.MethodsA total of 195 subjects; including 65 CRSwNP + AS patients, 99 CRSwNP-alone patients, and 31 healthy control subjects; were enrolled in the study. Nasal tissues from patients with CRSwNP + AS, CRSwNP-alone and control subjects were assessed for infiltration of inflammatory cells and concentrations of total IgE. Whole-transcriptome sequencing was performed and differentially expressed (DE) mRNAs and long non-coding RNAs (lncRNAs) and their associated pathways were analyzed. The correlations between type 2 cytokines and local eosinophils, tissue IgE, and transcriptome signatures were evaluated.ResultsSignificantly higher local eosinophil infiltration and higher levels of total IgE were found in nasal tissues from CRSwNP + AS patients than in nasal tissues from CRSwNP-alone patients. Furthermore, atopy and recurrence were significantly more frequent in patients with CRSwNP + AS than in patients with CRSwNP-alone (62.5% vs 28.6% and 66.7% vs 26.9%, respectively). RNA sequencing analysis identified 1988 common DE-mRNAs, and 176 common DE-lncRNAs shared by CRSwNP + AS versus control and CRSwNP-alone versus control. Weighted gene coexpression network analysis (WGCNA) identified LINC01146 as hub lncRNA dysregulated in both subtypes of CRSwNP. Overall, 968 DE-mRNAs and 312 DE-lncRNAs were identified between CRSwNP + AS and CRSwNP-alone. Both pathway enrichment analysis and WGCNA indicated that the phenotypic traits of CRSwNP + AS were mainly associated with higher activities of arachidonic acid metabolism, type 2 cytokines related pathway and fibrinolysis pathway, and lower activity of IL-17 signalling pathway. Furthermore, the expression of type 2 cytokines; IL5 and IL13, was positively correlated with local eosinophil infiltration, tissue IgE level, and the expression of DE-mRNAs that related to arachidonic acid metabolism. Moreover, WGCNA identified HK3-006 as hub lncRNA in yellow module that most positively correlated with phenotypic traits of CRSwNP + AS.ConclusionsPatients with CRSwNP + AS have distinct type 2-high inflammation-associated molecular signatures in nasal tissues compared to patients with CRSwNP-alone.