Combined blood and pleural levels of mesothelin and osteopontin for the diagnosis of malignant pleural mesothelioma

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor with poor survival rate. It is difficult to diagnose MPM at an early stage. Soluble mesothelin remains the best available biomarker for MPM, however the lack of sensitivity for early stage disease provides a motivation for the search of an additional marker that could be combined with mesothelin for early malignancy detection. Aim of work: The aim was to evaluate the diagnostic value of soluble mesothelin and osteopontin both in blood and pleural fluid of MPM patients and to assess whether combination of these markers could improve the diagnostic accuracy of mesothelin. Methodology: In this study mesothelin and osteopontin were measured by ELISA method in 197 samples (123 blood and 74 pleural) obtained from 123 participants, divided into 4 groups: 38 MPM patients, 24 patients with metastatic pleural effusion (Mets) of various carcinomas, 29 patients with hydrothorax and 32 healthy asbestos exposed subjects. Receiver operating characteristic (ROC) curves were generated to compare the diagnostic capability of these biomarkers. Combination of markers was done through logistic regression analysis. Results: The median blood and pleural levels of the two markers were significantly higher in MPM patients than in hydrothorax or asbestos exposure groups (P < 0.0001), however the difference between MPM and Mets group was not significant. Combining the data from blood mesothelin and osteopontin using logistic regression model raised the area under the ROC curve (AUC) from 0.774 for serum mesothelin and 0.828 for plasma osteopontin to 0.867 to differentiate MPM from hydrothorax and asbestos exposed subjects. Combining the diagnostic capability of both pleural markers raised the AUC from 0.871 for pleural mesothelin and 0.847 for pleural osteopontin to 0.905 to differentiate MPM from hydrothorax patients. Conclusion: The performance of serum and pleural mesothelin in diagnosing MPM was improved when combined with plasma and pleural osteopontin (respectively) through logistic regression analysis model. This will be a great advance in screening and management of MPM.