A combination of protein biomarkers may effectively distinguish malignant from non-malignant pleural effusions, according to the results of a recent study, “Identifying Thoracic Malignancies Through Pleural Fluid Biomarkers: A Predictive Multivariate Model,” published in the journal Medicine.
Malignant pleural effusion is a condition characterized by the buildup of extra fluid in the pleural space, which is the space between the lungs and the chest wall. The condition arises as a consequence of cancer, with lung and breast cancer accounting for the majority of cases (from 50 percent to 65 percent).
Diagnosing malignant pleural effusions is performed by pleural fluid cytological examination. The cytological yield may vary, however, and finding pleural fluid biomarkers of malignancy would allow a more specific diagnosis, avoiding the need for additional invasive procedures.
A research team at the Arnau de Vilanova University Hospital, in Lleida, Spain, aimed to identify candidate biomarkers that exhibit differential expression in the pleural fluid of patients with mesothelioma, lung adenocarcinoma, lymphoma, and tuberculosis.
The researchers used a multiplex protein biochip with 120 biomarkers to determine the protein content of the pleural fluid from samples of 29 mesotheliomas, 29 lung adenocarcinomas, 12 lymphomas, and 35 tuberculosis. The team used the relative abundance of the selected biomarkers to distinguish malignant versus benign tuberculosis effusions, lung adenocarcinoma versus mesothelioma, and lymphoma versus tuberculosis.
Significant profile differences were found in the expression of metalloproteinase-9 (MMP-9), cathepsin-B, C-reactive protein, and chondroitin sulfate to distinguish malignant from tuberculosis effusions. Further analysis showed that these proteins carry 85 percent sensitivity, and 100 percent specificity.
Discriminating lung adenocarcinoma from mesothelioma combining CA19-9, CA15-3, and kallikrein-12 expression led to 65 percent sensitivity and 100 percent specificity. Using cathepsin-B only resulted in 89 percent sensitivity and 62 percent specificity in distinguishing between lymphomatous and tuberculosis effusions, a moderate result. However, when a patient’s age was also taken into consideration, cathepsin-B profile improved to 72 percent sensitivity and 100 percent specificity.
In conclusion, researchers suggested that a panel of four biomarkers — MMP-9, cathepsin-B, C-reactive protein, and chondroitin sulfate — present in pleural fluid samples can discriminate with high confidence a malignant versus tuberculosis effusion, and three biomarkers — CA19-9, CA15-3, kallikrein-12 – can differentiate lung adenocarcinoma from mesothelioma. Additionally, cathepsin-B together with patient’s age could also help discriminate between lymphomatous versus tuberculosis effusion.