20.500.12556/DiRROS-19358 Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases Background Asbestos exposure is associated with increased risk of several diseases, including malignant mesothelioma (MM). Cell surface glycoprotein mesothelin is overexpressed in MM and serum soluble mesothelin-related peptides (SMRP) were already proposed as a diagnostic or prognostic biomarker in MM. However, interindividual variability in serum SMRP levels limits the clinical usefulness. Our primary objective was to investigate the influence of MSLN rs1057147 on serum SMRP levels in asbestos-exposed subjects and patients with asbestos-related diseases as well as on survival in MM. Subjects and methods Among 782 asbestos-exposed subjects and patients with asbestos-related diseases, 154 had MM. Serum SMRP levels were determined using sandwich enzyme-linked immunosorbent assay. All subjects were genotyped for MSLN rs1057147 polymorphism using competitive allele-specific polymerase chain reaction. Nonparametric tests, logistic and Cox regression were used in statistical analysis to compare different subject groups. Results MM patients had significantly higher SMRP levels than all other subjects (p < 0.001). Compared to wild-type MSLN rs1057147 genotype, both heterozygotes and carriers of two polymorphic alleles had significantly higher SMRP levels among subjects without MM (p < 0.001), but not in MM patients (p = 0.424). If genotype information was included, specificity of SMRP increased from 88.5% to 92.7% for the optimal cutoff value. Overall survival was significantly shorter in MM patients carrying at least one polymorphic rs1057147 allele (HR = 1.72, 95% CI = 1.15-2.55, p = 0.008). Conclusions MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of MM patients. Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients. asbestos-related disease malignant mesothelioma mesothelin azbestna bolezen maligni mezoteliom mezotelin true false true Association of Radiology and Oncology Ljubljana Angleški jezik Slovenski jezik by Authors Neznano 2024-07-16 11:15:19 2024-07-16 11:15:19 2024-07-17 03:59:14 0000-00-00 00:00:00 2020 0 0 Soavtorji: Viljem Kovac, Metoda Dodic-Fikfak, Vita Dolzan and Alenka Franko; str. 86-95, IX no. 1 Vol. 54 Mar. 2020 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 2020-03-01 616-057 1318-2099 10.2478/raon-2020-0011 34748377 https://content.sciendo.com/view/journals/raon/54/1/article-p86.xml?tab_body=pdf-69320 1 2aa3718e-4343-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26692 RAZ_Goricar_Katja_2020.pdf RAZ_Goricar_Katja_2020.pdf 1 01CC8C6E238AD275AAFD78F5F5BE1D38 e6a7b3a0c74348090bd7b8373828e8f7e57e4bb084daaf4475185b6ce020c1dd 51269071-4343-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=26693 Onkološki inštitut Ljubljana 0 0 0