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Profiling Tumor-Associated Markers for Early Detection of Malignant Mesothelioma: An Epidemiologic Study

¹ Department of Molecular Pathology and Innovative Therapies, Clinic of Occupational Medicine, Polytechnic University of Marche, Ancona, Italy; ² Department of Medical Oncology, Hospital University of Ancona, Ancona, Italy; ³ Department of Anaesthesiology, IRCCS Orthopaedic Institute "Rizzoli," Bologna, Italy; ⁴ Apoptosis Research Group, School of Medical Science, Griffith University, Southport, Queensland, Australia; and ⁵ Molecular Therapy Group, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Requests for reprints: Marco Tomasetti, Department of Molecular Pathology and Innovative Therapies, Polytechnic University of Marche, via Tronto 10/A, Torrette di Ancona, 60020 Ancona, Italy. Phone: 39-071-2206062; Fax: 39-071-2206182. E-mail: m.tomasetti{at}univpm.it

Improved detection methods for diagnosis of asymptomatic malignant mesothelioma (MM) are essential for an early and reliable detection and treatment of this type of neoplastic disease. Thus, focus has been on finding tumor markers in the blood that can be used for noninvasive detection of MM. Ninety-four asbestos-exposed subjects defined at high risk, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the clinical significance of 8-hydroxy-2'-deoxyguanosine (8OHdG) in WBCs and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors [platelet-derived growth factor β, hepatocyte growth factor, basic fibroblast growth factor, and vascular endothelial growth factor β (VEGFβ)], and matrix proteases [matrix metalloproteinase (MMP) 2, MMP9, tissue inhibitor of metalloproteinase (TIMP) 1, and TIMP2] for potential early detection of MM. The area under receiver operating characteristic (ROC) curves indicate that 8OHdG levels can discriminate asbestos-exposed subjects from healthy controls but not from MM patients. Significant area under ROC curve values were found for SMRPs, discriminating asbestos-exposed subjects from MM patients but not from healthy controls. Except for platelet-derived growth factor β, the hepatocyte growth factor, basic fibroblast growth factor, and VEGFβ can significantly differentiate high-risk individuals from healthy control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, and TIMP2. In addition to the diagnostic performance defined by the ROC analysis, the sensitivity and specificity results of markers with clinical significance were calculated at defined cutoffs. The combination of 8OHdG, VEGFβ, and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations. (Cancer Epidemiol Biomarkers Prev 2008;17(1):163–70)