Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA, 02115, USA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Respir Res. 2022 Apr 21;23(1):97. doi: 10.1186/s12931-022-02013-w.
Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are characterized by shared exposures and clinical features, but distinct genetic and pathologic features exist. These features have not been well-studied using large-scale gene expression datasets. We hypothesized that there are divergent gene, pathway, and cellular signatures between COPD and IPF.
We performed RNA-sequencing on lung tissues from individuals with IPF (n = 231) and COPD (n = 377) compared to control (n = 267), defined as individuals with normal spirometry. We grouped the overlapping differential expression gene sets based on direction of expression and examined the resultant sets for genes of interest, pathway enrichment, and cell composition. Using gene set variation analysis, we validated the overlap group gene sets in independent COPD and IPF data sets.
We found 5010 genes differentially expressed between COPD and control, and 11,454 genes differentially expressed between IPF and control (1% false discovery rate). 3846 genes overlapped between IPF and COPD. Several pathways were enriched for genes upregulated in COPD and downregulated in IPF; however, no pathways were enriched for genes downregulated in COPD and upregulated in IPF. There were many myeloid cell genes with increased expression in COPD but decreased in IPF. We found that the genes upregulated in COPD but downregulated in IPF were associated with lower lung function in the independent validation cohorts.
We identified a divergent gene expression signature between COPD and IPF, with increased expression in COPD and decreased in IPF. This signature is associated with worse lung function in both COPD and IPF.
慢性阻塞性肺疾病（COPD）和特发性肺纤维化（IPF）的特征是具有共同的暴露和临床特征，但存在明显的遗传和病理特征。这些特征尚未通过大规模基因表达数据集进行很好的研究。我们假设 COPD 和 IPF 之间存在不同的基因、途径和细胞特征。
我们对来自 IPF（n=231）和 COPD（n=377）患者与对照组（n=267）的肺组织进行了 RNA 测序，对照组定义为肺功能正常的个体。我们根据表达方向对重叠的差异表达基因集进行分组，并检查感兴趣基因、途径富集和细胞组成的结果集。使用基因集变异分析，我们在独立的 COPD 和 IPF 数据集中验证了重叠组基因集。
我们发现 COPD 与对照之间有 5010 个基因差异表达，IPF 与对照之间有 11454 个基因差异表达（1%的假发现率）。3846 个基因在 IPF 和 COPD 之间重叠。一些途径富含 COPD 上调和 IPF 下调的基因；然而，没有途径富含 COPD 下调和 IPF 上调的基因。许多髓样细胞基因在 COPD 中表达增加，而在 IPF 中表达减少。我们发现，在 COPD 中上调而在 IPF 中下调的基因与独立验证队列中较低的肺功能相关。
我们确定了 COPD 和 IPF 之间的一个不同的基因表达特征，COPD 中表达增加，而 IPF 中表达减少。该特征与 COPD 和 IPF 中肺功能下降相关。
