Identification of Novel Markers for the Diagnosis of Malignant Pleural Mesothelioma

Abstract

The diagnosis of malignant pleural mesothelioma is difficult, with the most common differential diagnoses being benign pleural diseases and metastatic adenocarcinomas (ADCA). To identify novel markers that would be able to improve diagnostic accuracy, we performed a genome-wide gene expression analysis on tumor cell lines established from pleural effusions (malignant pleural mesothelioma and lung ADCA). This analysis led to the identification of genes encoding novel and pertinent cellular and soluble markers, for which the expression was validated by real-time RT-PCR. Immunohistochemical staining of tumor biopsy specimens with anti-type III collagen antibodies showed positive labeling for mesothelioma cells but not for ADCA cells. Using enzyme-linked immunosorbent assay, we showed that the C-C motif chemokine 2 (CCL2) concentration was significantly higher in pleural effusions from patients with mesothelioma (n = 61) than in subjects with ADCA (n = 25) or with benign pleural effusions (n = 15): median (interquartile range) = 2.99 ng/ml (1.76 to 6.01) vs 0.99 ng/ml (0.51 to 1.83) and 1.47 ng/ml (0.80 to 1.56), respectively, P < 0.0001. Conversely, the galectin-3 concentration was lower in mesothelioma: 11.50 ng/ml (6.73 to 23.53) vs 24.74 ng/ml (20.42 to 70.35) and 17.64 ng/ml (14.81 to 24.68), respectively, P < 0.0001. The areas under the curve for CCL2 were 0.8030 and 0.7716 for the differentiation of mesothelioma from ADCA or benign pleural effusions, respectively. Similarly, the areas under the curve obtained for galectin-3 were 0.7980 and 0.6923, respectively. In conclusion, type III collagen, CCL2, and galectin-3 are promising new diagnostic markers for mesothelioma.

Molecular Classification of Malignant Pleural Mesothelioma: Identification of a Poor Prognosis Subgroup Linked to the Epithelial-to-Mesenchymal Transition

“…In this study, our discovery cohort was based on MPM in culture, which has the considerable advantage of focusing on the tumor cells, without interference from the tumor microenvironment. To date, the largest transcriptomic studies by microarray on MPM in culture used 10 and 13 independent samples (38,39). In our study, we used 67 different MPM in culture and 108 frozen tumor samples to validate the classification; this makes our study one of the largest in terms of MPM samples.…”

Measles Virus Vaccine–Infected Tumor Cells Induce Tumor Antigen Cross-Presentation by Human Plasmacytoid Dendritic Cells

“…The mesothelioma Meso13 cell line was established and characterized in our laboratory (26), the melanoma M18 was a kind gift from Dr. Labarriere [Institut National de la Sant e et de la Recherche Medicale (INSERM) U892, Nantes, France], and the pulmonary adenocarcinoma A549 cell line was purchased from ATCC (Manassas, VA). All cell lines were cultured at 37 C, 5% CO 2 atmosphere in RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum, 100 U/mL penicillin, 100 mg/mL streptomycin and 2 mmol/L L-glutamine (all reagents were purchased from Gibco-Invitrogen, Cergy-Pontoise, France).…”

A 5-aza-2'-deoxycytidine/valproate combination induces cytotoxic T-cell response against mesothelioma

“…Human epithelioid mesothelioma cell lines were established from pleural effusions in our laboratory [22]. The human melanoma cell line M117 was provided by N. Labarrière (INSERM, U892, Nantes, France).…”