Abstract. Malignant mesothelioma (MM) is a highly aggressive tumor associated with asbestos exposure. The identification of a marker specific for MM may be of considerable value for the early detection of this tumor and may be used in particular to screen groups with a history of asbestos exposure. The aim of this study was to evaluate serum soluble mesothelin-related peptide (SMRP) levels as a diagnostic marker for MM and investigate whether its diagnostic value is enhanced by combination with other biomarkers. Serum SMRP levels were measured using a quantitative enzyme-linked immunosorbent assay in 96 patients with MM, 55 patients with lung cancer and 39 individuals with a history of asbestos exposure. Receiver operating characteristic curves were constructed for performance evaluation. Stepwise logistic regression analysis was used to select marker combinations (MCs). Serum SMRP levels in patients with MM were significantly higher compared to those in the other groups (P<0.001). The sensitivity of SMRP levels in diagnosing MM was 56% and its specificity for MM vs. lung cancer and individuals with asbestos exposure was 87 and 92%, respectively. The area under the curve (AUC) was 0.76 [95% confidence interval (CI): 0.68-0.83] for the differentiation between MM and lung cancer and 0.78 (95% CI: 0.71-0.86) for the differentiation between MM and individuals with asbestos exposure. For the MC of presence of effusion, SMRP and carcinoembryonic antigen (CEA) levels, the AUC for the differentiation between MM and lung cancer (0.92; 95% CI: 0.88-0.97) and the differentiation between MM and individuals with asbestos exposure (0.93; 95% CI: 0.87-1.0) was significantly higher compared to that for SMRP alone (P= 0.0001 and 0.0058, respectively). While the specificity of this MC was comparable to SMRP alone, its sensitivity was ~20% higher compared to that of SMRP alone. Therefore, combining SMRP and CEA improves the diagnostic performance of SMRP alone. A combination of serum biomarkers, including SMRP, may facilitate the non-invasive diagnosis of MM.
IntroductionMalignant mesothelioma (MM) is a tumor that develops from the serous membranes that line the body cavities and it may arise in the pleura, peritoneum and pericardium; in addition, although extremely rare, it may also develop in the tunica vaginalis testis. The most common form of this disease is the malignant pleural mesothelioma (MPM). MM was previously considered as being extremely rare; however, its incidence and associated mortality rate exhibited a sharp increase worldwide over the last 50 years, due to the close association of MM with asbestos exposure. The prognosis of MPM is poor, with a median survival of ~9-17 months (1). However, in selected patients with epithelioid tumor histology, early-stage disease, who undergo trimodality treatment (combination of chemotherapy, postoperative radiotherapy and extrapleural pneumonectomy), median overall survival of 51 months and 5-year survival rates of 46% have been reported (2). Recent phase II trials reported a m...