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Pleural fluids associated with metastatic lung tumors are rich in progelatinase B/proMMP-9
J Kotyza1, M Pesek, V Bednárová
1Department of Biochemistry, Medical Faculty in Pilsen, Charles University, 30166 Pilsen, Czech Republic. jaromir.kotyza@lfp.cuni.cz
Abstract:
Gelatinase B/MMP-9 is a member of matrix metalloproteinases with a major role in extracellular matrix degradation, cell proliferation and migration. Its proenzyme form has also been reported in pleural fluids as an inducible species, but its relation to pleural pathology has not yet been fully clarified. The primary goal of this study was to evaluate proMMP-9 as a potential marker for differentiating pleural effusions of both malignant and non-malignant origin. Pleural fluid samples were studied from 194 patients, including tumor etiology in 133 cases, inflammatory disorders in 33, transudates in 12, and unspecified disorders in 16 patients. The concentrations of proMMP-9 were estimated by means of immunoassays and/or by scanning zymography. Samples were also examined for C-reactive protein (CRP). The analysis of proMMP-9 showed significant differences among the etiological groups with the highest concentrations in para-inflammatory exudates, intermediate in para-neoplastic exudates, and the lowest in transudates. However, the analysis of the para-neoplastic group revealed a distinct heterogeneity with a minor portion of fluids reaching values typical for para-inflammatory effusions. A subsequent sorting based on tumor histology showed increased levels particularly in exudates associated with metastatic tumors. Interestingly, proMMP-9 values in general correlated with CRP, a systemic marker of inflammation. Thus, MMP-9 proenzyme appears to complement traditional markers distinguishing pleural fluids of different origin. Yet, the differentiation between paraneoplastic and para-inflammatory exudates must be regarded with caution due to the presence of a high-expressive paraneoplastic sub-population, including effusions associated with metastatic tumors.
Insights
Proenzyme matrix metalloproteinase-9 (proMMP-9) levels in pleural fluid can help distinguish malignant from non-malignant effusions. Elevated proMMP-9 is seen in inflammatory and metastatic tumors, complementing C-reactive protein (CRP) markers.
Area of Science:
- Biochemistry
- Oncology
- Pulmonology
Background:
- Matrix metalloproteinases (MMPs), specifically MMP-9 (Gelatinase B), are crucial in extracellular matrix remodeling, influencing cell behavior.
- The role of proenzyme MMP-9 in pleural effusions and its diagnostic utility in pleural pathology remain incompletely understood.
- Pleural effusions present diagnostic challenges, necessitating improved biomarkers for accurate etiological classification.
Purpose of the Study:
- To investigate proMMP-9 as a biomarker for differentiating malignant and non-malignant pleural effusions.
- To assess the correlation between proMMP-9 levels and specific etiological categories of pleural effusions.
- To compare proMMP-9 concentrations with C-reactive protein (CRP) in pleural fluid analysis.
Main Methods:
- Analysis of pleural fluid samples from 194 patients with diverse etiologies (malignant, inflammatory, transudative).
- Quantification of proMMP-9 concentrations using immunoassays and/or scanning zymography.
- Measurement of C-reactive protein (CRP) levels in parallel with proMMP-9.
Main Results:
- Significant differences in proMMP-9 levels were observed across etiological groups: highest in para-inflammatory, intermediate in para-neoplastic, and lowest in transudates.
- Paraneoplastic effusions exhibited heterogeneity, with some showing levels comparable to para-inflammatory effusions, particularly those linked to metastatic tumors.
- ProMMP-9 levels generally correlated positively with CRP, indicating a link to systemic inflammation.
Conclusions:
- ProMMP-9 shows promise as a complementary biomarker for distinguishing pleural fluid origins, aiding in the diagnosis of pleural effusions.
- Caution is advised when differentiating paraneoplastic from para-inflammatory effusions due to overlapping proMMP-9 expression, especially in metastatic disease.
- The study highlights proMMP-9's potential role in understanding pleural fluid pathobiology and improving diagnostic accuracy.
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