Tracking breast cancer progression using Methylscape.

Cancer progression is driven by epigenetic reprogramming, where promoter hypermethylation of tumour-suppressor genes and global hypomethylation reshape gene regulation and cellular phenotypes, promoting oncogenesis and disease advancement. We previously introduced the Methylscape, a cancer-specific DNA methylation landscape characterized by clustered promoter hypermethylation and gene body hypomethylation that enhances DNA's physical affinity for gold surfaces. Here, we demonstrate that Methylscape can be leveraged to monitor cancer progression. In a TGF-β-induced breast cancer epithelial-mesenchymal transition (EMT) model, we observe increased Methylscape enrichment of mesenchymal-state DNA, indicating that this method can sensitively detect subtle epigenetic remodelling linked to tumour progression. Using a gold-based DNA desorption enrichment strategy coupled with methylation sequencing and qPCR, we show that hypermethylated regions are preferentially enriched on gold surface. Finally, we developed a low-cost, disposable screen-printed electrode platform for stage-specific breast cancer monitoring. Together, these findings establish Methylscape as a promising biophysical biomarker for non-invasive, real-time monitoring of cancer progression, advancing its potential for clinical translation.