Diagnostic Value of Six Tumor Markers for Malignant Pleural Effusion in 1,230 Patients: A Single-Center Retrospective Study

Background: The diagnostic value of tumor markers in pleural effusion (PE) and serum for malignant pleural effusion (MPE) is still in debate. This study aimed to evaluate the diagnostic value of six tumor markers in PE, serum, and the corresponding PE/serum (PE/S) ratio in distinguishing MPE from benign pleural effusion (BPE). Methods: A total of 1,230 patients with PE (452 MPEs and 778 BPEs) were retrospectively included in the study. PE and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), cytokeratin 19 fragment (CYFRA 21-1), and neuron-specific enolase (NSE) were measured. The area under the curve (AUC) was used to assess the single and combined diagnostic values of the six tumor markers for MPE. Results: The levels of the six tumor markers in PE, serum, and PE/S were significantly higher in MPE than that in BPE, except for serum CA125. PE CEA showed the highest AUC [0.890 (0.871–0.907)] at a cut-off value of 3.7 ng/ml compared to any single tumor marker using receiver operating characteristic (ROC) analysis. The specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of PE CEA were 74.1%, 95.5%, 90.5%, 86.4%, 16.47, and 0.27, respectively. The combination of PE CEA and serum CYFRA21-1 showed the best diagnostic performance with an AUC of 0.934 (sensitivity, 79.9%; specificity, 95.7%, PPV, 90.5; PLR, 17.35) among all two or three combinations. Besides, serum CYFRA21-1 was the best diagnostic tumor marker in distinguishing cytology-negative MPE from BPE at a cut-off value of 3.0 ng/ml. Conclusion: PE CEA was the best diagnostic tumor marker in distinguishing MPE from BPE. Serum CYFRA21-1 was the best diagnostic tumor marker in distinguishing cytology-negative MPE from BPE. The combination of PE CEA and serum CYFRA21-1 could increase the diagnostic performance in distinguishing MPE from BPE and cytology-negative MPE from BPE.