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

• Published in: International journal of molecular sciences 2022-03, Vol.23 (7), p.3717
• Main Authors: Panagopoulou, Maria, Drosouni, Andrianna, Fanidis, Dionysiοs, Karaglani, Makrina, Balgkouranidou, Ioanna, Xenidis, Nikolaos, Aidinis, Vassilis, Chatzaki, Ekaterini
• Format: Article
• Language: English
• Subjects: Biomarkers; Biomarkers - metabolism; Biopsy; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Cell-Free Nucleic Acids - metabolism; Correlation; DNA Methylation; Epigenetics; Female; Gene Expression; Humans; Liquid Biopsy; Lysophosphatidic acid; Medical prognosis; Metastases; Metastasis; Methylation; Pathogenesis; Phosphodiesterase; Phosphoric Diester Hydrolases - genetics; Phosphoric Diester Hydrolases - metabolism; Pyrophosphatase; Transcription
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23073717

Autotaxin (ATX), encoded by the ctonucleotide pyrophosphatase/phosphodiesterase 2 ( ) gene, is a key enzyme in lysophosphatidic acid (LPA) synthesis. We have recently described 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 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.