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ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker

Autotaxin (ATX), encoded by the ctonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) gene, is a key enzyme in lysophosphatidic acid (LPA) synthesis. We have recently described ENPP2 methylation profiles in health and multiple malignancies and demonstrated correlation to its aberrant expression....

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Autores principales: Panagopoulou, Maria, Drosouni, Andrianna, Fanidis, Dionysiοs, Karaglani, Makrina, Balgkouranidou, Ioanna, Xenidis, Nikolaos, Aidinis, Vassilis, Chatzaki, Ekaterini
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998992/
https://www.ncbi.nlm.nih.gov/pubmed/35409077
http://dx.doi.org/10.3390/ijms23073717
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author Panagopoulou, Maria
Drosouni, Andrianna
Fanidis, Dionysiοs
Karaglani, Makrina
Balgkouranidou, Ioanna
Xenidis, Nikolaos
Aidinis, Vassilis
Chatzaki, Ekaterini
author_facet Panagopoulou, Maria
Drosouni, Andrianna
Fanidis, Dionysiοs
Karaglani, Makrina
Balgkouranidou, Ioanna
Xenidis, Nikolaos
Aidinis, Vassilis
Chatzaki, Ekaterini
author_sort Panagopoulou, Maria
collection PubMed
description Autotaxin (ATX), encoded by the ctonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) gene, is a key enzyme in lysophosphatidic acid (LPA) synthesis. We have recently described ENPP2 methylation profiles in health and multiple malignancies and demonstrated correlation to its aberrant expression. Here we focus on breast cancer (BrCa), analyzing in silico publicly available BrCa methylome datasets, to identify differentially methylated CpGs (DMCs) and correlate them with expression. Numerous DMCs were identified between BrCa and healthy breast tissues in the gene body and promoter-associated regions (PA). PA DMCs were upregulated in BrCa tissues in relation to normal, in metastatic BrCa in relation to primary, and in stage I BrCa in relation to normal, and this was correlated to decreased mRNA expression. The first exon DMC was also investigated in circulating cell free DNA (ccfDNA) isolated by BrCa patients; methylation was increased in BrCa in relation to ccfDNA from healthy individuals, confirming in silico results. It also differed between patient groups and was correlated to the presence of multiple metastatic sites. Our data indicate that promoter methylation of ENPP2 arrests its transcription in BrCa and introduce first exon methylation as a putative biomarker for diagnosis and monitoring which can be assessed in liquid biopsy.
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spelling pubmed-89989922022-04-12 ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker Panagopoulou, Maria Drosouni, Andrianna Fanidis, Dionysiοs Karaglani, Makrina Balgkouranidou, Ioanna Xenidis, Nikolaos Aidinis, Vassilis Chatzaki, Ekaterini Int J Mol Sci Article Autotaxin (ATX), encoded by the ctonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) gene, is a key enzyme in lysophosphatidic acid (LPA) synthesis. We have recently described ENPP2 methylation profiles in health and multiple malignancies and demonstrated correlation to its aberrant expression. Here we focus on breast cancer (BrCa), analyzing in silico publicly available BrCa methylome datasets, to identify differentially methylated CpGs (DMCs) and correlate them with expression. Numerous DMCs were identified between BrCa and healthy breast tissues in the gene body and promoter-associated regions (PA). PA DMCs were upregulated in BrCa tissues in relation to normal, in metastatic BrCa in relation to primary, and in stage I BrCa in relation to normal, and this was correlated to decreased mRNA expression. The first exon DMC was also investigated in circulating cell free DNA (ccfDNA) isolated by BrCa patients; methylation was increased in BrCa in relation to ccfDNA from healthy individuals, confirming in silico results. It also differed between patient groups and was correlated to the presence of multiple metastatic sites. Our data indicate that promoter methylation of ENPP2 arrests its transcription in BrCa and introduce first exon methylation as a putative biomarker for diagnosis and monitoring which can be assessed in liquid biopsy. MDPI 2022-03-28 /pmc/articles/PMC8998992/ /pubmed/35409077 http://dx.doi.org/10.3390/ijms23073717 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Panagopoulou, Maria
Drosouni, Andrianna
Fanidis, Dionysiοs
Karaglani, Makrina
Balgkouranidou, Ioanna
Xenidis, Nikolaos
Aidinis, Vassilis
Chatzaki, Ekaterini
ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker
title ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker
title_full ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker
title_fullStr ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker
title_full_unstemmed ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker
title_short ENPP2 Promoter Methylation Correlates with Decreased Gene Expression in Breast Cancer: Implementation as a Liquid Biopsy Biomarker
title_sort enpp2 promoter methylation correlates with decreased gene expression in breast cancer: implementation as a liquid biopsy biomarker
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8998992/
https://www.ncbi.nlm.nih.gov/pubmed/35409077
http://dx.doi.org/10.3390/ijms23073717
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