Abstract
Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4–4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome furthers our understanding of malignant mesothelioma, identified galectin 1 as a potential diagnostic biomarker, and highlighted several possible prognostic biomarkers of this disease.
Highlights
From the ‡Department of Laboratory Medicine, Division of Pathology, Karolinska Institutet, Stockholm, Sweden SE-141 86; ¶Cancer Proteomics, Mass Spectrometry, SciLifeLab Stockholm, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden SE-171 21; ʈChest Diseases Department, Eskisehir Osmangazi University, Eskisehir, Turkey TR-264 80
Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma
Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma
Summary
Identification of soluble biomarkers of malignant mesothelioma in pleural effusions might complement the morphological examination and shorten the time needed to reach a conclusive diagnosis. New Mesothelioma Effusion Biomarkers ating factor or N-ERC/mesothelin) These fragments have similar diagnostic capabilities [4], with moderate specificity and sensitivity for malignant mesothelioma [5,6,7,8,9,10]. Hyaluronan is synthesized by mesothelial cells, and high levels in mesothelioma effusions were noted as far back as the early 1940s [16] This linear polysaccharide is produced in the cell membrane and has a high specificity, but only moderate sensitivity, for mesothelioma (7, 16 –25)
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