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Variation rs2235503 C>A within the promoter of MSLN affects transcriptional rate of mesothelin and plasmatic levels of the soluble mesothelin-related peptide
  • +13
  • Roberto Silvestri,
  • Perla Pucci,
  • Chiara De Santi,
  • Irene Dell'Anno,
  • Simona Miglietta,
  • Alda Corrado,
  • Vanessa Nicolì,
  • Daniela Marolda,
  • Monica Cipollini,
  • Enrica Pellegrino,
  • Monica Evangelista,
  • Alessandra Bonotti,
  • Rudy Foddis,
  • Alfonso Cristaudo,
  • Stefano Landi,
  • Federica Gemignani
Roberto Silvestri
University of Pisa
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Perla Pucci
The Open University
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Chiara De Santi
Royal College of Surgeons in Ireland
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Irene Dell'Anno
University of Pisa
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Simona Miglietta
IRCCS San Raffaele Scientific Institute
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Alda Corrado
University of Milan
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Vanessa Nicolì
University of Pisa
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Daniela Marolda
University of Pisa
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Monica Cipollini
University of Pisa
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Enrica Pellegrino
University of Pisa
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Monica Evangelista
CNR di Pisa
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Alessandra Bonotti
Pisa University Hospital
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Rudy Foddis
University of Pisa
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Alfonso Cristaudo
University of Pisa
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Stefano Landi
University of Pisa, University of Pisa
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Federica Gemignani
University of Pisa
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Abstract

Soluble mesothelin-related peptide (SMRP) is a promising biomarker for malignant pleural mesothelioma (MPM), but several confounding factors can reduce SMRP-based tests accuracy. The identification of these confounders could improve the diagnostic performance of SMRP. In this study, we evaluated the sequence of 1000 base pairs encompassing the minimal promoter region of MSLN gene to identify expression quantitative trait loci (eQTL) that can affect SMRP. We assessed the association between four MSLN promoter variants and SMRP levels in a cohort of 72 MPM and 677 non-MPM subjects, and we carried out in vitro assays to investigate their functional role. Our results show that rs2235503 is an eQTL for MSLN associated with increased levels of SMRP in non-MPM subjects. Furthermore, we show that this polymorphic site affects the accuracy of SMRP, highlighting the importance of evaluating the individual’s genetic background and giving novel insights to refine SMRP specificity as a diagnostic biomarker.