Respiratory Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
West China Biobanks, Department of Clinical Research Management, West China Hospital, Sichuan University, Chengdu, China.
FEBS Open Bio. 2021 Apr;11(4):1237-1249. doi: 10.1002/2211-5463.13127. Epub 2021 Mar 7.
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and fixed airflow obstruction. Patients with COPD have increased risk of lung cancer (LC), and the coexistence of both diseases is associated with poorer survival. However, the mechanisms predisposing patients with COPD to LC development and poor prognosis remain unclear. Gene expression profiles were downloaded from the Gene Expression Omnibus. Twenty-two data sets were included (n = 876). We identified 133 DEGs and 145 DEGs in patients with COPD and LC compared with healthy controls, respectively. There were 1544 DEGs in patients with LC and coexisting COPD compared with COPD, and these DEGs are mainly involved in the cell cycle, DNA replication, p53 signalling and insulin signalling. The biological processes primarily associated with these DEGs are oxidation reduction and apoptosis. SPP1 was the only overlapping DEG that was up-regulated in patients with COPD and/or LC, and this was validated by qPCR in an independent cohort. The area under the curve value for SPP1 was 0.893 (0.822-0.963) for the prediction of LC in patients with COPD. High expression of SPP1 in patients with LC was associated with shorter survival time. Up-regulation of SPP1 may be associated with increased risk of LC in patients with COPD and therefore may have potential as a therapeutic target for LC in patients with COPD.
慢性阻塞性肺疾病（COPD）的特征是持续的气道炎症和固定的气流阻塞。COPD 患者患肺癌（LC）的风险增加，这两种疾病并存与生存率降低有关。然而，导致 COPD 患者易患 LC 发展和预后不良的机制仍不清楚。从基因表达综合数据库中下载了基因表达谱。共纳入 22 个数据集（n=876）。我们分别在 COPD 和 LC 患者与健康对照者中鉴定出 133 个 DEGs 和 145 个 DEGs。在 LC 患者与单纯 COPD 患者相比，有 1544 个 DEGs，这些 DEGs 主要涉及细胞周期、DNA 复制、p53 信号和胰岛素信号。与这些 DEGs 主要相关的生物学过程是氧化还原和细胞凋亡。在 COPD 和/或 LC 患者中上调的唯一重叠 DEG 是 SPP1，在独立队列中通过 qPCR 进行了验证。在 COPD 患者中，SPP1 的曲线下面积值（AUC）为 0.893（0.822-0.963），用于预测 LC。在 LC 患者中 SPP1 高表达与生存时间较短相关。SPP1 的上调可能与 COPD 患者 LC 风险增加有关，因此可能有作为 COPD 患者 LC 治疗靶点的潜力。
