Hou Zhifei, Zhang Xinran, Gao Yong, Geng Jing, Jiang Yu, Dai Huaping, Wang Chen
Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Center for Respiratory Medicine; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Pharmgenomics Pers Med. 2023 Jun 1;16:537-549. doi: 10.2147/PGPM.S409644. eCollection 2023.
Coal worker's pneumoconiosis (CWP) is a chronic occupational disease mainly caused by coal dust inhalation in miners. This study aimed to investigate the clinical value of Osteopontin (OPN), KL-6, Syndecan-4 and Gremlin-1 as serum biomarkers in CWP.
We integrated reported lung tissues transcriptome data in pneumoconiosis patients with silica-exposed alveolar macrophage microarray data to identify four CWP-associated serum biomarkers. The serum concentrations of Osteopontin, Krebs von den Lungen-6 (KL-6), Syndecan-4 and Gremlin-1 were measured in 100 healthy controls (HCs), 100 dust-exposed workers (DEWs) and 200 patients of CWP. Receiver operating characteristic (ROC) curve analysis was used to determine the sensitivity, specificity, cut-off value and area under the curve (AUC) value of biomarkers.
The pulmonary function parameters decreased sequentially, and the serum OPN, KL-6, Syndecan-4 and Gremlin-1 concentrations were increased sequentially among the HC, DEW and CWP groups. Among all participants, multivariable analysis revealed that these four biomarkers were negatively correlated with the pulmonary function parameters (all <0.05). Compared with HCs, patients with higher OPN, KL-6, Syndecan-4 and Gremlin-1 had higher risk for CWP. The combination of OPN, KL-6, and Syndecan-4 can improve the diagnostic sensitivity and specificity of CWP patients differentiated from HCs or DEWs.
OPN, KL-6 and Syndecan-4 are novel biomarkers that can be used for CWP auxiliary diagnosis. The combination of three biomarkers can improve the diagnostic values of CWP.
煤工尘肺（CWP）是一种主要由矿工吸入煤尘引起的慢性职业病。本研究旨在探讨骨桥蛋白（OPN）、KL-6、多功能蛋白聚糖-4（Syndecan-4）和Gremlin-1作为CWP血清生物标志物的临床价值。
我们整合了已报道的尘肺患者肺组织转录组数据和二氧化硅暴露肺泡巨噬细胞微阵列数据，以识别四种与CWP相关的血清生物标志物。测定了100名健康对照者（HCs）、100名粉尘暴露工人（DEWs）和200名CWP患者血清中骨桥蛋白、克雷伯斯-冯-登-伦根-6（KL-6）、多功能蛋白聚糖-4和Gremlin-1的浓度。采用受试者工作特征（ROC）曲线分析来确定生物标志物的敏感性、特异性、临界值和曲线下面积（AUC）值。
肺功能参数在HC、DEW和CWP组中依次降低，血清OPN、KL-6、多功能蛋白聚糖-4和Gremlin-1浓度依次升高。在所有参与者中，多变量分析显示这四种生物标志物与肺功能参数呈负相关（均<0.05）。与HCs相比，OPN、KL-6、多功能蛋白聚糖-4和Gremlin-1水平较高的患者患CWP的风险更高。OPN、KL-6和多功能蛋白聚糖-4联合使用可提高CWP患者与HCs或DEWs鉴别的诊断敏感性和特异性。
OPN、KL-6和多功能蛋白聚糖-4是可用于CWP辅助诊断的新型生物标志物。三种生物标志物联合使用可提高CWP的诊断价值。
