Zhang Huohuo, Wu Jiaxuan, Gan Jiadi, Wang Wei, Liu Yi, Song Tingting, Yang Yongfeng, Ji Guiyi, Li Weimin
Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Institute of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Thorac Cancer. 2025 Jan;16(1):e15517. doi: 10.1111/1759-7714.15517.
Chronic obstructive pulmonary disease (COPD) is confirmed as an independent risk factor for the development of lung cancer. Although low-dose CT screening significantly reduces the mortality rate of lung cancer, the misdiagnosis and missed diagnosis rates remain high in the COPD population. Additionally, several COPD patients are unable to undergo invasive histological examinations. Therefore, there is an urgent need for minimally invasive biomarkers to screen or diagnose lung cancer in COPD patients. In this study, peripheral blood samples were collected from COPD patients with and without lung cancer. Plasma exosomes (EVs) were extracted for proteomic analysis. Sixteen differentially expressed proteins (DEPs) were preliminarily selected via label-free quantification (LFQ) proteomic technology and comprehensive bioinformatics analysis. Parallel reaction monitoring (PRM) targeted validation identified five candidate proteins associated with COPD with lung cancer. Compared to the COPD group, KRT1, KRT9, and KRT10 were significantly upregulated in the COPD with lung cancer group, while GPLD1 and TF were downregulated. The biomarkers identified in our study provide a foundation for non-invasive screening and diagnosis of lung cancer in COPD patients and exploration of the mechanisms shared between COPD and lung cancer.
慢性阻塞性肺疾病（COPD）被确认为肺癌发生的独立危险因素。尽管低剂量CT筛查显著降低了肺癌死亡率，但在COPD人群中误诊和漏诊率仍然很高。此外，一些COPD患者无法接受侵入性组织学检查。因此，迫切需要微创生物标志物来筛查或诊断COPD患者的肺癌。在本研究中，收集了患有和未患有肺癌的COPD患者的外周血样本。提取血浆外泌体（EVs）进行蛋白质组学分析。通过无标记定量（LFQ）蛋白质组学技术和综合生物信息学分析初步筛选出16种差异表达蛋白（DEP）。平行反应监测（PRM）靶向验证确定了5种与COPD合并肺癌相关的候选蛋白。与COPD组相比，KRT1、KRT9和KRT10在COPD合并肺癌组中显著上调，而GPLD1和TF下调。我们研究中鉴定出的生物标志物为COPD患者肺癌的非侵入性筛查和诊断以及探索COPD和肺癌之间的共同机制提供了基础。
