Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin – a case-control comparison nested into a prospective cohort of asbestos-exposed workers

• Published in: Scientific reports 2018-09, Vol.8 (1), p.14321-11, Article 14321
• Main Authors: Johnen, Georg, Burek, Katarzyna, Raiko, Irina, Wichert, Katharina, Pesch, Beate, Weber, Daniel G., Lehnert, Martin, Casjens, Swaantje, Hagemeyer, Olaf, Taeger, Dirk, Brüning, Thomas
• Format: Article
• Language: English
• Subjects: 631/67/2322; 692/499; 692/53/2421; 692/699/67/1641; 82/1; 82/80; Aged; Aged, 80 and over; Asbestos; Asbestos - adverse effects; Calbindin 2 - blood; Calretinin; Case-Control Studies; Cohort Studies; Diagnosis; Female; GPI-Linked Proteins - blood; Health risk assessment; Humanities and Social Sciences; Humans; Immunoassays; Incidence; Lung Neoplasms - blood; Lung Neoplasms - chemically induced; Lung Neoplasms - diagnosis; Male; Mesothelioma; Mesothelioma - blood; Mesothelioma - chemically induced; Mesothelioma - diagnosis; Mesothelioma, Malignant; Middle Aged; multidisciplinary; Occupational exposure; Occupational Exposure - adverse effects; Prognosis; Prospective Studies; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-32315-3

Malignant mesothelioma (MM) is strongly associated with a previous asbestos exposure. To improve timely detection of MM in asbestos workers, better screening tools – like minimally-invasive biomarkers – are desirable. Between 2008 and 2018 2,769 patients with benign asbestos-related diseases were recruited to participate in annual screens. Using a nested case-control design the protein markers calretinin and mesothelin were determined by enzyme-linked immunosorbent assays in prediagnostic plasma samples of 34 MM cases as well as 136 matched controls from the cohort. Conditional on a pre-defined specificity of 98% for calretinin and 99% for mesothelin the markers reached individual sensitivities of 31% and 23%, respectively, when including the incident cases with samples taken between one and 15 months before diagnosis. The combination of both markers increased the sensitivity to 46% at 98% specificity. Marker complementation increased with earlier sampling. The marker combination improves the sensitivity of the individual markers, indicating a useful complementation and suggesting that additional markers may further improve the performance. This is the first prospective cohort study to evaluate a detection of MM by calretinin and its combination with mesothelin up to about a year before clinical diagnosis. Whether an earlier diagnosis will result in reduced mortality has yet to be demonstrated.