Liu W, Wang K, Guan H, Ma L, Cui Y, Liu C, Shi J, Fan Y, Sun Y
Department of Otolaryngology, the Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Department of Otolaryngology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Rhinology. 2024 Dec 1;62(6):739-749. doi: 10.4193/Rhin24.248.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic sinonasal disease characterized by heterogeneous inflammation. However, the presence of systemic inflammation heterogeneity in CRSwNP patients remains unknown. This study aims to profile transcriptomic alterations in the blood of CRSwNP patients and characterize the CRSwNP heterogeneity based on blood transcriptomic biomarkers.
Patients with CRSwNP were prospectively recruited from three hospitals and chronologically divided into exploratory (n=123) and independent validation (n=46) cohorts. Transcriptomic profiles were generated by whole blood mRNA sequencing and subjected to patient clustering, differential expression, and pathway analysis. Differences in immune pattern and clinicopathologic features between clusters were assessed. A transcriptomic signature was defined and applied to an independent cohort to validate the findings.
CRSwNP patients showed diverse blood transcriptomic profiles versus healthy controls, or when stratified by tissue and blood eosinophils and asthma comorbidity. Transcriptome-wide correlation analysis revealed a transcriptional signature associated with blood eosinophil levels, consisting of nine T2-related genes (CLC, SIGLEC8, ALOX15, IL5RA, PTGDR2, CCL23, CCR3, EPX and IL1RL1). Three distinct clusters with differing systemic eosinophilic and neutrophilic inflammation patterns and asthma comorbidity were identified based on transcriptomic profiling of T2 and T1/3-related blood biomarkers. A 36-gene signature was developed by machine learning and accurately predicted the three CRSwNP subtypes. Validation on an independent cohort confirmed the prediction robustness.
There is heterogeneous systemic inflammation associated with eosinophilic and neutrophilic patterns in patients with CRSwNP. Endotyping based on blood transcriptomic biomarkers might lead to more personalized treatment strategies for CRSwNP in the future.
伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）是一种以异质性炎症为特征的慢性鼻窦疾病。然而，CRSwNP患者全身炎症异质性的存在情况仍不清楚。本研究旨在分析CRSwNP患者血液中的转录组改变，并基于血液转录组生物标志物对CRSwNP的异质性进行特征描述。
从三家医院前瞻性招募CRSwNP患者，并按时间顺序分为探索性队列（n = 123）和独立验证队列（n = 46）。通过全血mRNA测序生成转录组图谱，并进行患者聚类、差异表达和通路分析。评估各聚类之间免疫模式和临床病理特征的差异。定义一个转录组特征并应用于独立队列以验证研究结果。
与健康对照相比，或按组织和血液嗜酸性粒细胞及哮喘合并症分层时，CRSwNP患者表现出多样的血液转录组图谱。全转录组相关性分析揭示了一种与血液嗜酸性粒细胞水平相关的转录特征，由九个与2型相关的基因（CLC、SIGLEC8、ALOX15、IL5RA、PTGDR2、CCL23、CCR3、EPX和IL1RL1）组成。基于2型和1/3型相关血液生物标志物的转录组分析，鉴定出三个具有不同全身嗜酸性粒细胞和中性粒细胞炎症模式及哮喘合并症的不同聚类。通过机器学习开发了一个36基因特征，并准确预测了三种CRSwNP亚型。在独立队列上的验证证实了预测的稳健性。
CRSwNP患者存在与嗜酸性粒细胞和中性粒细胞模式相关的异质性全身炎症。基于血液转录组生物标志物的内型分类可能会在未来为CRSwNP带来更个性化的治疗策略。
