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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.

Published version
Peer-reviewed

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Authors

Silvestri, Roberto 
De Santi, Chiara 
Dell'Anno, Irene 
Miglietta, Simona 

Abstract

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.

Description

Keywords

diagnostic biomarkers, eQTL, fluorescent reporter assay, malignant pleural mesothelioma, single nucleotide polymorphisms, soluble mesothelin-related peptide

Journal Title

Front Genet

Conference Name

Journal ISSN

1664-8021
1664-8021

Volume Title

11

Publisher

Frontiers Media SA