Exosomal proteins as biomarkers for differential diagnosis of pleural effusion etiologies.

e20508 Background: The clinical need for differential diagnosis of pleural effusion etiologies remains unmet. This study aimed to identify exosomal proteins from lung cancer-related pleural effusion (LCPE), tuberculous pleural effusion (TPE), and parapneumonic pleural effusion (PPE) and evaluate their diagnostic value. Methods: A total of 47 pleural effusion samples were collected. Exosomes were extracted. Bioinformatics was employed to assess differential protein expression and functional pathways, while ROC curves evaluated the diagnostic significance of these proteins. Validation of the differential proteins was conducted on an expanded sample set (46 LCPE, 23 TPE, 9 PPE) via ELISA. Results: A total of 772 proteins that are expressed in both LCPE, TPE and PPE were identified. Based on our analysis and literature research, 18 candidate biomarkers were selected. Validation using Parallel Reaction Monitoring (PRM) analysis and ELISA showed that TLN1, APOH, and PSMD8 were significantly overexpressed in LCPE compared to TPE and PPE (P < 0.05), while SYWC was overexpressed in TPE (P < 0.05). ROC analysis demonstrated excellent diagnostic accuracy of the combination of TLN1, APOH, PSMD8, and SYWC in differentiating LCPE from TPE (AUC = 0.953, 95% CI: 0.891-1.00), especially in cases with CEA < 15 ug/L in PE. The combination of HPTR, ANT3, and TLN1 effectively distinguished LCPE from PPE (AUC = 0.933, 95% CI: 0.837-1.00). ELISA further confirmed the diagnostic utility of the TLN1, SYWC, and APOH combination in distinguishing LCPE from TPE (AUC = 0.969, 95% CI: 0.935-1.00), with SYWC exhibiting remarkable accuracy in solely differentiating TPE from PPE (AUC = 100%). Conclusions: Ourstudy identified and validated pleural effusion exosomal protein biomarkers with significant diagnostic potential. The combinations of TLN1, APOH and SYWC, or ANT3, HPTR and TLN1, can serve as biomarkers for differentiating LCPE from TPE or PPE.