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Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases

Katja Goricar

Katja Goricar

Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Goricar, Katja
, 
Viljem Kovac

Viljem Kovac

  • Institute of Oncology LjubljanaLjubljana, Slovenia
  • Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Kovac, Viljem
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Metoda Dodic-Fikfak

Metoda Dodic-Fikfak

  • Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
  • Clinical Institute of Occupational Medicine, University Medical Centre LjubljanaLjubljana, Slovenia
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Dodic-Fikfak, Metoda
, 
Vita Dolzan

Vita Dolzan

Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Dolzan, Vita
 e 
Alenka Franko

Alenka Franko

  • Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
  • Clinical Institute of Occupational Medicine, University Medical Centre LjubljanaLjubljana, Slovenia
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Franko, Alenka
  
07 mar 2020
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Categoria dell'articolo: research article
Pubblicato online: 07 mar 2020
Pagine: 86 - 95
DOI: https://doi.org/10.2478/raon-2020-0011
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© 2020 Katja Goricar, Viljem Kovac, Metoda Dodic-Fikfak, Vita Dolzan, Alenka Franko, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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.

Lingua:
Inglese
Frequenza di pubblicazione:
4 volte all'anno
Argomenti della rivista:
Medicina, Medicina clinica, Medicina interna, Ematologia, Oncologia, Radiologia
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