The University of British Columbia Centre for Heart Lung Innovation (HLI), St Paul's Hospital, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
Respir Res. 2019 Aug 5;20(1):176. doi: 10.1186/s12931-019-1147-2.
Effects of systemic corticosteroids on blood gene expression are largely unknown. This study determined gene expression signature associated with short-term oral prednisone therapy in patients with chronic obstructive pulmonary disease (COPD) and its relationship to 1-year mortality following an acute exacerbation of COPD (AECOPD).
Gene expression in whole blood was profiled using the Affymetrix Human Gene 1.1 ST microarray chips from two cohorts: 1) a prednisone cohort with 37 stable COPD patients randomly assigned to prednisone 30 mg/d + standard therapy for 4 days or standard therapy alone and 2) the Rapid Transition Program (RTP) cohort with 218 COPD patients who experienced AECOPD and were treated with systemic corticosteroids. All gene expression data were adjusted for the total number of white blood cells and their differential cell counts.
In the prednisone cohort, 51 genes were differentially expressed between prednisone and standard therapy group at a false discovery rate of < 0.05. The top 3 genes with the largest fold-changes were KLRF1, GZMH and ADGRG1; and 21 genes were significantly enriched in immune system pathways including the natural killer cell mediated cytotoxicity. In the RTP cohort, 27 patients (12.4%) died within 1 year after hospitalisation of AECOPD; 32 of 51 genes differentially expressed in the prednisone cohort significantly changed from AECOPD to the convalescent state and were enriched in similar cellular immune pathways to that in the prednisone cohort. Of these, 10 genes including CX3CR1, KLRD1, S1PR5 and PRF1 were significantly associated with 1-year mortality.
Short-term daily prednisone therapy produces a distinct blood gene signature that may be used to determine and monitor treatment responses to prednisone in COPD patients during AECOPD.
The prednisone cohort was registered at clinicalTrials.gov ( NCT02534402 ) and the RTP cohort was registered at ClinicalTrials.gov ( NCT02050022 ).
全身皮质类固醇对血液基因表达的影响在很大程度上尚不清楚。本研究确定了与慢性阻塞性肺疾病（COPD）患者短期口服泼尼松治疗相关的基因表达特征，及其与 COPD 急性加重（AECOPD）后 1 年死亡率的关系。
使用 Affymetrix Human Gene 1.1 ST 微阵列芯片对来自两个队列的全血基因表达进行分析：1）泼尼松队列，共 37 例稳定期 COPD 患者随机分为泼尼松 30mg/d+标准治疗 4 天组或标准治疗组；2）快速过渡计划（RTP）队列，共 218 例经历 AECOPD 并接受全身皮质类固醇治疗的 COPD 患者。所有基因表达数据均根据白细胞总数及其差异细胞计数进行调整。
在泼尼松队列中，与标准治疗组相比，泼尼松组有 51 个基因在假发现率 < 0.05 时有差异表达。差异最大的前 3 个基因是 KLRF1、GZMH 和 ADGRG1；21 个基因显著富集在免疫系统途径中，包括自然杀伤细胞介导的细胞毒性。在 RTP 队列中，27 例（12.4%）患者在 AECOPD 住院后 1 年内死亡；在泼尼松队列中差异表达的 51 个基因中有 32 个在 AECOPD 至恢复期发生显著变化，并与泼尼松队列中的细胞免疫途径相似。其中，包括 CX3CR1、KLRD1、S1PR5 和 PRF1 在内的 10 个基因与 1 年死亡率显著相关。
短期每日泼尼松治疗可产生独特的血液基因特征，可用于确定和监测 AECOPD 期间 COPD 患者对泼尼松的治疗反应。
泼尼松队列在 clinicalTrials.gov 上注册（NCT02534402），RTP 队列在 clinicalTrials.gov 上注册（NCT02050022）。
