DNA Methylation Profiling of Colorectal Cancer Liver Metastasis: Identification of Core Biomarkers and Functional Pathways

Ayvaz Ş., İnan C., Batan N.

European Human Genetics Conference (ESHG 2026), Gothenburg, Sweden, 13 - 16 June 2026, pp.1, (Summary Text)

  • Publication Type: Conference Paper / Summary Text
  • City: Gothenburg
  • Country: Sweden
  • Page Numbers: pp.1
  • Karadeniz Technical University Affiliated: Yes

Abstract

Background: DNA methylation is a key epigenetic regulator of gene expression and is implicated in cancer metastasis. Colorectal cancer (CRC) commonly spreads to the liver, yet methylation signatures that distinguish metastatic lesions from primary liver tumors remain incompletely defined. We aimed to identify differentially methylated genes (DMGs), enriched pathways, and candidate diagnostic biomarkers for CRC liver metastasis.

Material and Methods: DNA methylation data were obtained from GEO (GSE28094), including normal liver tissue, primary liver tumors, and colon-to-liver metastatic samples. DMGs were identified using limma with multiple-testing correction. Functional interpretation was performed using GO and KEGG enrichment analyses. A protein–protein interaction network was used to prioritize hub genes, and diagnostic performance was assessed by ROC analysis.

Results: Metastatic samples displayed a distinct methylation profile with substantially more DMGs than primary liver tumors. Hypermethylated DMGs were enriched in PI3K–Akt and MAPK signaling, whereas hypomethylated DMGs were associated with immune-related processes, including cytokine interactions. Network analysis highlighted CTNNB1, AKT1, and EGFR as prominent hubs. ROC analysis supported high discriminatory performance of these candidates in separating metastatic tissue from primary liver tumors.

Conclusion: CRC liver metastasis shows a characteristic DNA methylation signature with pathway-level dysregulation and hub genes that may serve as methylation-based biomarkers. These findings support the utility of methylation profiling for molecular stratification of liver lesions and motivate validation in independent cohorts.

Keywords: DNA methylation; colorectal cancer; liver metastasis; biomarkers; epigenetics