Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide
Soluble mesothelin-related peptide (SMRP) is a promising biomarker for malignant pleural mesothelioma (MPM), but several confounding factors can reduce SMRP-based test’s accuracy. The identification of these confounders could improve the diagnostic performance of SMRP. In this study, we evaluated th...
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| Format: | Article |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2020.00975/full |
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| author | Roberto Silvestri Perla Pucci Perla Pucci Chiara De Santi Chiara De Santi Irene Dell’Anno Simona Miglietta Simona Miglietta Alda Corrado Alda Corrado Vanessa Nicolí Vanessa Nicolí Daniela Marolda Monica Cipollini Enrica Pellegrino Monica Evangelista Alessandra Bonotti Rudy Foddis Alfonso Cristaudo Stefano Landi Federica Gemignani |
| author_facet | Roberto Silvestri Perla Pucci Perla Pucci Chiara De Santi Chiara De Santi Irene Dell’Anno Simona Miglietta Simona Miglietta Alda Corrado Alda Corrado Vanessa Nicolí Vanessa Nicolí Daniela Marolda Monica Cipollini Enrica Pellegrino Monica Evangelista Alessandra Bonotti Rudy Foddis Alfonso Cristaudo Stefano Landi Federica Gemignani |
| author_sort | Roberto Silvestri |
| collection | DOAJ |
| description | Soluble mesothelin-related peptide (SMRP) is a promising biomarker for malignant pleural mesothelioma (MPM), but several confounding factors can reduce SMRP-based test’s accuracy. The identification of these confounders could improve the diagnostic performance of SMRP. In this study, we evaluated the sequence of 1,000 base pairs encompassing the minimal promoter region of the 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. |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-22T12:41:16Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-fa1be331a6b945f292d0a23b17377ebb2022-12-21T18:25:27ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-08-011110.3389/fgene.2020.00975558867Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related PeptideRoberto Silvestri0Perla Pucci1Perla Pucci2Chiara De Santi3Chiara De Santi4Irene Dell’Anno5Simona Miglietta6Simona Miglietta7Alda Corrado8Alda Corrado9Vanessa Nicolí10Vanessa Nicolí11Daniela Marolda12Monica Cipollini13Enrica Pellegrino14Monica Evangelista15Alessandra Bonotti16Rudy Foddis17Alfonso Cristaudo18Stefano Landi19Federica Gemignani20Department of Biology, University of Pisa, Pisa, ItalyDepartment of Biology, University of Pisa, Pisa, ItalyDivision of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, United KingdomDepartment of Biology, University of Pisa, Pisa, ItalyDepartment of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, IrelandDepartment of Biology, University of Pisa, Pisa, ItalyDepartment of Biology, University of Pisa, Pisa, ItalySan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), San Raffaele Scientific Institute (IRCCS), Milan, ItalyDepartment of Biology, University of Pisa, Pisa, ItalyDepartment of Bioscience, University of Milan, Milan, ItalyDepartment of Biology, University of Pisa, Pisa, ItalyDepartment of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, ItalyDepartment of Biology, University of Pisa, Pisa, ItalyDepartment of Biology, University of Pisa, Pisa, ItalyDepartment of Biology, University of Pisa, Pisa, ItalyInstitute of Clinical Physiology (IFC), CNR, Pisa, ItalyPreventive and Occupational Medicine, University Hospital of Pisa, Pisa, ItalyDepartment of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, ItalyDepartment of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Pisa, ItalyDepartment of Biology, University of Pisa, Pisa, ItalyDepartment of Biology, University of Pisa, Pisa, ItalySoluble mesothelin-related peptide (SMRP) is a promising biomarker for malignant pleural mesothelioma (MPM), but several confounding factors can reduce SMRP-based test’s accuracy. The identification of these confounders could improve the diagnostic performance of SMRP. In this study, we evaluated the sequence of 1,000 base pairs encompassing the minimal promoter region of the 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.https://www.frontiersin.org/article/10.3389/fgene.2020.00975/fullsoluble mesothelin-related peptidemalignant pleural mesotheliomadiagnostic biomarkerssingle nucleotide polymorphismsfluorescent reporter assayeQTL |
| spellingShingle | Roberto Silvestri Perla Pucci Perla Pucci Chiara De Santi Chiara De Santi Irene Dell’Anno Simona Miglietta Simona Miglietta Alda Corrado Alda Corrado Vanessa Nicolí Vanessa Nicolí Daniela Marolda Monica Cipollini Enrica Pellegrino Monica Evangelista Alessandra Bonotti Rudy Foddis Alfonso Cristaudo Stefano Landi Federica Gemignani Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide Frontiers in Genetics soluble mesothelin-related peptide malignant pleural mesothelioma diagnostic biomarkers single nucleotide polymorphisms fluorescent reporter assay eQTL |
| title | Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide |
| title_full | Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide |
| title_fullStr | Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide |
| title_full_unstemmed | Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide |
| title_short | Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide |
| title_sort | variation rs2235503 c a within the promoter of msln affects transcriptional rate of mesothelin and plasmatic levels of the soluble mesothelin related peptide |
| topic | soluble mesothelin-related peptide malignant pleural mesothelioma diagnostic biomarkers single nucleotide polymorphisms fluorescent reporter assay eQTL |
| url | https://www.frontiersin.org/article/10.3389/fgene.2020.00975/full |
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