Title : Pleural fluid C-C motif chemokine ligand 2: An effective biomarker for diagnosing malignant pleural effusion
Abstract:
Background: Accurate diagnosis of malignant pleural effusion (MPE) using biomarkers remains challenging. C-C motif chemokine ligand 2 (CCL2), a chemokine markedly overexpressed under pathological conditions, has emerged as a pivotal biomarker across various diseases and plays a key role in the immune response associated with MPE. This study aimed to evaluate the diagnostic accuracy of CCL2 for MPE.
Methods: From June 2019 to April 2022, 170 patients with exudative pleural effusion admitted to our hospital were enrolled and randomly divided into a training cohort (71.8%, n = 122) and an internal validation cohort (28.2%, n = 48). Clinical indicators, including pleural fluid carcinoembryonic antigen (CEA), were collected. Pleural fluid CCL2 concentrations were determined using enzyme-linked immunosorbent assay. Analyses included receiver operating characteristic (ROC) curves, univariate logistic regression, and nomogram construction. Model performance was evaluated by the area under the ROC curve (AUC), concordance index (c-index), and calibration plots.
Results: Pleural fluid CCL2 levels were significantly higher in MPE than in non-MPE cases (cut-off value = 234.73 pg/mL, AUC = 0.754, sensitivity = 95.6%), whereas adenosine deaminase (ADA) levels were lower. Compared with other pleural fluid biochemical indicators, pleural fluid CCL2 showed competitive diagnostic accuracy, particularly for exclusion diagnosis (negative predictive value = 94.4%). In addition, CCL2 exerts a significant stratification effect on the diagnosis of MPE subgroups, especially in the ADA ≥ 26.5 U/L group, chloride ≥ 109.25 mmol/L group, and CEA ≥ 2.62 ng/mL group, where its diagnostic efficacy is more prominent. A nomogram incorporating pleural fluid CCL2, age, and ADA achieved AUCs exceeding 0.9 in both the training and validation cohorts (c-index = 0.974). Calibration curves demonstrated strong agreement between predicted and observed probabilities of MPE.
Conclusion: Pleural fluid CCL2 is an effective biomarker for diagnosing MPE. The CCL2-based nomogram represents a robust, minimally invasive tool for accurate identification of MPE.
