AUTHOR=Silvestri Roberto , Pucci Perla , De Santi Chiara , Dell’Anno Irene , Miglietta Simona , Corrado Alda , Nicolí Vanessa , Marolda Daniela , Cipollini Monica , Pellegrino Enrica , Evangelista Monica , Bonotti Alessandra , Foddis Rudy , Cristaudo Alfonso , Landi Stefano , Gemignani Federica 

TITLE=Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00975

DOI=10.3389/fgene.2020.00975

ISSN=1664-8021

ABSTRACT=<p>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 <italic>MSLN</italic> gene to identify expression quantitative trait loci (eQTL) that can affect SMRP. We assessed the association between four <italic>MSLN</italic> promoter variants and SMRP levels in a cohort of 72 MPM and 677 non-MPM subjects, and we carried out <italic>in vitro</italic> assays to investigate their functional role. Our results show that rs2235503 is an eQTL for <italic>MSLN</italic> 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.</p>