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Updated: Oct 13, 2025
Methylated DNA Immunoprecipitation
Published on: January 2, 2009
ENPP2 Methylation in Health and Cancer
Maria Panagopoulou1, Dionysios Fanidis2, Vassilis Aidinis2
1Laboratory of Pharmacology, Medical School, Democritus University of Thrace, GR-68100 Alexandroupolis, Greece.
Abstract:
Autotaxin (ATX) encoded by Ectonucleotide Pyrophosphatase/Phosphodiesterase 2 (ENPP2) is a key enzyme in Lysophosphatidic Acid (LPA) synthesis implicated in cancer. Although its aberrant expression has been reported, ENPP2 methylation profiles in health and malignancy are not described. We examined in silico the methylation of ENPP2 analyzing publicly available methylome datasets, to identify Differentially Methylated CpGs (DMCs) which were then correlated with expression at gene and isoform levels. Significance indication was set to be FDR corrected p-value < 0.05. Healthy tissues presented methylation in all gene body CGs and lower levels in Promoter Associated (PA) regions, whereas in the majority of the tumors examined (HCC, melanoma, CRC, LC and PC) the methylation pattern was reversed. DMCs identified in the promoter were located in sites recognized by multiple transcription factors, suggesting involvement in gene expression. Alterations in methylation were correlated to an aggressive phenotype in cancer cell lines. In prostate and lung adenocarcinomas, increased methylation of PA CGs was correlated to decreased ENPP2 mRNA expression and to poor prognosis parameters. Collectively, our results corroborate that methylation is an active level of ATX expression regulation in cancer. Our study provides an extended description of the methylation status of ENPP2 in health and cancer and points out specific DMCs of value as prognostic biomarkers.
Insights
Autotaxin (ATX) enzyme ENPP2 methylation patterns differ between healthy and cancerous tissues. Promoter methylation changes in ENPP2 correlate with cancer aggressiveness and poor prognosis, highlighting its role in cancer regulation.
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Autotaxin (ATX), encoded by ENPP2, is crucial for lysophosphatidic acid (LPA) synthesis and is implicated in cancer.
- Aberrant ATX expression is noted in cancers, but ENPP2 methylation profiles in health and disease remain undescribed.
Purpose of the Study:
- To investigate the in silico methylation profiles of ENPP2 in healthy and malignant tissues.
- To identify Differentially Methylated CpGs (DMCs) and correlate them with ENPP2 gene and isoform expression.
- To assess the association between ENPP2 methylation, cancer aggressiveness, and patient prognosis.
Main Methods:
- In silico analysis of publicly available methylome datasets.
- Identification of Differentially Methylated CpGs (DMCs) using FDR corrected p-value < 0.05.
- Correlation analysis between DMCs, ENPP2 expression (mRNA and isoform levels), and clinicopathological parameters.
Main Results:
- Healthy tissues showed gene body methylation with low promoter-associated (PA) methylation.
- Most tumors (HCC, melanoma, CRC, LC, PC) exhibited reversed methylation patterns (high promoter, low gene body).
- Promoter DMCs were located in transcription factor binding sites, suggesting regulatory roles.
- Increased PA CG methylation in prostate and lung adenocarcinomas correlated with decreased ENPP2 mRNA and poor prognosis.
Conclusions:
- DNA methylation is an active regulatory mechanism for ATX (ENPP2) expression in cancer.
- This study provides a comprehensive description of ENPP2 methylation status across various cancers.
- Identified DMCs hold potential as prognostic biomarkers for cancer patients.
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