title: 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.
authors.affiliation: INSERM U892, Centre de Recherche en Cancérologie Nantes-Angers, Nantes, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gueugnon
authors.forename: Sabrina
authors.initials: S
authors.lastname: Leclercq
authors.forename: Christophe
authors.initials: C
authors.lastname: Blanquart
authors.forename: Christine
authors.initials: C
authors.lastname: Sagan
authors.forename: Laurent
authors.initials: L
authors.lastname: Cellerin
authors.forename: Martine
authors.initials: M
authors.lastname: Padieu
authors.forename: Christian
authors.initials: C
authors.lastname: Perigaud
authors.forename: Arnaud
authors.initials: A
authors.lastname: Scherpereel
authors.forename: Marc
authors.initials: M
authors.lastname: Gregoire
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D016000:Cluster Analysis; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D005260:Female; D037502:Galectin 3 / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008654:Mesothelioma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D016066:Pleural Effusion, Malignant / Q000235:genetics / Q000473:pathology; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor; C111835:CCL2 protein, human; C439971:COL3A1 protein, human; D018932:Chemokine CCL2; D024061:Collagen Type III; D037502:Galectin 3