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Background <p>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).</p> Methods <p>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 &gt; 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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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The exosomal protein biomarkers auxiliary in diagnosis of interstitial lung disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月1日

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  • 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

摘要

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.