The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease
Abstract Background Exosome liquid biopsies might be a good supplement for early diagnosis of interstitial lung disease (ILD), especially those challenging cases such as connective tissue disease-ILD (CTD-ILD). Methods We developed a circulating exosomal proteomic signature to identify novel biomark...
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| Language: | English |
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BMC
2025-08-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-025-03326-2 |
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| author | Ming Dong Gaolei Hu Xi Chen Lingling Zhang Yuxiao Zhang Yanting Fang Shuilin Liao Yukai Wang Qian Li Peiyan Zheng Bingpeng Guo Tinpou Lai Qun Luo Huimin Huang Qian Han Baoqing Sun |
| author_facet | Ming Dong Gaolei Hu Xi Chen Lingling Zhang Yuxiao Zhang Yanting Fang Shuilin Liao Yukai Wang Qian Li Peiyan Zheng Bingpeng Guo Tinpou Lai Qun Luo Huimin Huang Qian Han Baoqing Sun |
| author_sort | Ming Dong |
| collection | DOAJ |
| description | Abstract Background Exosome liquid biopsies might be a good supplement for early diagnosis of interstitial lung disease (ILD), especially those challenging cases such as connective tissue disease-ILD (CTD-ILD). Methods We developed a circulating exosomal proteomic signature to identify novel biomarkers of ILDs combined with high-resolution CT (HRCT) examination and a new method that makes exosome testing clinically feasible. Blood-derived exosomes were extracted and characterized using a centrifugal microfluidic disc system (Exo-CMDS)-based chemiluminescence immunoassay before being subjected to proteomic analysis by mass spectrometry. Significantly differentially expressed proteins (DEPs) were identified and validated in > 600 clinical samples (collected at three hospitals) by comparing the ILD and disease/healthy control groups. Multivariable logistic regression (LR) analysis was implemented to test the diagnostic performance of the selected biomarkers either alone or in combination. Results Candidate biomarkers KL-6, CAPN2, SP-B were selected from the top DEPs. An LR model that combined exosomal KL-6/CAPN2/SP-B levels performed well in both the discovery (AUC = 0.987, 95%CI = 0.975–0.998) and validation (AUC = 0.936, 95%CI = 0.911–0.960) sets. The LR model based on the three biomarkers exhibited markedly better diagnostic performance (AUC = 0.880, 95%CI = 0.834–0.925) in serum-KL-6-negative ILD, than the conventional serum-KL-6-based method and could also accurately diagnose connective tissue disease associated-ILD (CTD-ILD) in the context of CTD. Conclusion The circulating exosomal protein detection system used in this study represents a valuable tool for identifying promising exosomal biomarkers for ILD and holds promise for improving the diagnosis and prognosis of patients with ILD in the future. |
| format | Article |
| id | doaj-art-f12591bcad7f47a8ab2bc76d23aed4ad |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj-art-f12591bcad7f47a8ab2bc76d23aed4ad2025-08-20T04:03:02ZengBMCRespiratory Research1465-993X2025-08-0126111310.1186/s12931-025-03326-2The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung diseaseMing Dong0Gaolei Hu1Xi Chen2Lingling Zhang3Yuxiao Zhang4Yanting Fang5Shuilin Liao6Yukai Wang7Qian Li8Peiyan Zheng9Bingpeng Guo10Tinpou Lai11Qun Luo12Huimin Huang13Qian Han14Baoqing Sun15State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Clinical Laboratory, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Clinical Laboratory, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangdong Province, Guangzhou National LaboratoryGuangdong Province, Guangzhou National LaboratoryState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Clinical Laboratory, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Clinical Laboratory, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangdong Province, Guangzhou National LaboratoryDepartment of Rheumatology and Immunology, Shantou Central HospitalThe First Affiliated Hospital of Chongqing Medical and Pharmaceutical CollegeState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Clinical Laboratory, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangdong Province, Guangzhou National LaboratoryGuangdong Province, Guangzhou National LaboratoryState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Clinical Laboratory, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityGuangdong Province, Guangzhou National LaboratoryState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Clinical Laboratory, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical UniversityAbstract Background Exosome liquid biopsies might be a good supplement for early diagnosis of interstitial lung disease (ILD), especially those challenging cases such as connective tissue disease-ILD (CTD-ILD). Methods We developed a circulating exosomal proteomic signature to identify novel biomarkers of ILDs combined with high-resolution CT (HRCT) examination and a new method that makes exosome testing clinically feasible. Blood-derived exosomes were extracted and characterized using a centrifugal microfluidic disc system (Exo-CMDS)-based chemiluminescence immunoassay before being subjected to proteomic analysis by mass spectrometry. Significantly differentially expressed proteins (DEPs) were identified and validated in > 600 clinical samples (collected at three hospitals) by comparing the ILD and disease/healthy control groups. Multivariable logistic regression (LR) analysis was implemented to test the diagnostic performance of the selected biomarkers either alone or in combination. Results Candidate biomarkers KL-6, CAPN2, SP-B were selected from the top DEPs. An LR model that combined exosomal KL-6/CAPN2/SP-B levels performed well in both the discovery (AUC = 0.987, 95%CI = 0.975–0.998) and validation (AUC = 0.936, 95%CI = 0.911–0.960) sets. The LR model based on the three biomarkers exhibited markedly better diagnostic performance (AUC = 0.880, 95%CI = 0.834–0.925) in serum-KL-6-negative ILD, than the conventional serum-KL-6-based method and could also accurately diagnose connective tissue disease associated-ILD (CTD-ILD) in the context of CTD. Conclusion The circulating exosomal protein detection system used in this study represents a valuable tool for identifying promising exosomal biomarkers for ILD and holds promise for improving the diagnosis and prognosis of patients with ILD in the future.https://doi.org/10.1186/s12931-025-03326-2Interstitial lung diseaseLiquid biopsyExosomal biomarkerKrebs von den Lungen 6 |
| spellingShingle | Ming Dong Gaolei Hu Xi Chen Lingling Zhang Yuxiao Zhang Yanting Fang Shuilin Liao Yukai Wang Qian Li Peiyan Zheng Bingpeng Guo Tinpou Lai Qun Luo Huimin Huang Qian Han Baoqing Sun The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease Respiratory Research Interstitial lung disease Liquid biopsy Exosomal biomarker Krebs von den Lungen 6 |
| title | The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease |
| title_full | The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease |
| title_fullStr | The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease |
| title_full_unstemmed | The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease |
| title_short | The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease |
| title_sort | exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease |
| topic | Interstitial lung disease Liquid biopsy Exosomal biomarker Krebs von den Lungen 6 |
| url | https://doi.org/10.1186/s12931-025-03326-2 |
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