Abstract
Malignant pleural mesothelioma (MPM) is a highly aggressive and therapy resistant pleural malignancy that is caused by asbestos exposure. MPM is associated with poor prognosis and a short patient survival. The survival time is strongly influenced by the subtype of the tumor. Dyspnea and accumulation of pleural effusion in the pleural cavity are common symptoms of MPM. The diagnostic distinction from other malignancies and reactive conditions is done using histopathology or cytopathology, always supported by immunohistochemistry, and sometimes also by analyses of soluble biomarkers in effusion supernatant. We evaluated the soluble angiogenesis related molecules as possible prognostic and diagnostic biomarkers for MPM by Luminex multiplex assay. Pleural effusion from 42 patients with malignant pleural mesothelioma (MPM), 36 patients with adenocarcinoma (AD) and 40 benign (BE) effusions were analyzed for 10 different analytes that, in previous studies, were associated with angiogenesis, consisting of Angiopoietin-1, HGF, MMP-7, Osteopontin, TIMP-1, Galectin, Mesothelin, NRG1-b1, Syndecan-1 (SDC-1) and VEGF by a Human Premixed Multi-Analyte Luminex kit. We found that shed SDC-1 and MMP-7 levels were significantly lower, whereas Mesothelin and Galectin-1 levels were significantly higher in malignant mesothelioma effusions, compared to adenocarcinoma. Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1, NRG1-β1, VEGF and TIMP-1 were significantly higher in malignant pleural mesothelioma effusions compared to benign samples. Moreover, there is a negative correlation between Mesothelin and shed SDC-1 and positive correlation between VEGF, Angiopoietin-1 and shed SDC-1 level in the pleural effusion from malignant cases. Shed SDC-1 and VEGF have a prognostic value in malignant mesothelioma patients. Collectively, our data suggest that MMP-7, shed SDC-1, Mesothelin and Galectin-1 can be diagnostic and VEGF and SDC-1 prognostic markers in MPM patients. Additionally, Galectin-1, HGF, Mesothelin, MMP-7, Osteopontin, shed SDC-1 and TIMP-1 can be diagnostic for malignant cases.
Highlights
Malignant pleural mesothelioma (MPM) is an aggressive tumor of mesothelial origin that occurs after a long latency period following asbestos exposure often comprising several decades [1,2,3,4]
The aim of this study is to evaluate shed SDC-1 in pleural effusions together with angiogenesis related proteins and identify optimal biomarker batteries that allow earlier diagnosis and improve the possibilities to distinguish MPM from metastatic adenocarcinoma and reactive conditions
We did not find any significant correlation between all malignant cases, we showed a significant weak-positive correlation between shed SDC-1 and BAiomnoglieocupleosi2e0t2i0n,110,(xpFO= R0P.0E0E4R RaEnVdIErW= 0.3) and a significant weak-negative correlation between8 sohf 1e3d SDC-1 and Mesothelin (p = 0.004 and r = −0.3) (Figure 5)
Summary
Malignant pleural mesothelioma (MPM) is an aggressive tumor of mesothelial origin that occurs after a long latency period following asbestos exposure often comprising several decades [1,2,3,4]. This tumor occurs mostly in the pleura (>75%) and less often in the peritoneum (10–20%) or pericardium (1%) [5,6]. The median survival time of malignant pleural mesothelioma is less than 12 months [7] This survival is strongly influenced by subtype of the tumor and time of diagnosis [3,8].
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