Transforming Cancer Diagnostics: The Emergence of Liquid Biopsy and Epigenetic Markers

Abstract

Liquid biopsy represents a transformative approach in oncology, enabling noninvasive disease detection and monitoring through epigenetic signals in circulating tumor DNA (ctDNA), nucleosomes, and noncoding RNAs. Tumor initiation is driven by epigenetic modifications, including DNA methylation, histone alterations, and dysregulated noncoding RNAs, which disrupt gene regulation, cell cycle control, DNA repair, and metastatic processes. This review systematically examines recent evidence on DNA methylation, histone marks (e.g., H3K27me3, H3K18ac), and noncoding RNAs (miRNAs, lncRNAs) as biomarkers for early cancer detection, prognosis, and therapeutic response. Particular focus is placed on aberrant DNA methylation (e.g., hypermethylation of CDKN2A, RASSF1A) and altered histone modifications (e.g., EZH2-mediated silencing) as indicators of tumor heterogeneity and evolution. Stable and specific in biofluids, noncoding RNAs such as oncogenic miR-21, tumor-suppressive miR-34a, and metastasis-associated MALAT1/HOTAIR further enhance clinical applicability. Recent detection methods, including bisulfite sequencing, ChIP-seq, and RNA-seq, have advanced biomarker profiling, though challenges remain in standardization and low-abundance detection. With over 12 active clinical studies validating their utility, integration of epigenetic markers with AI and multiomics holds promise for individualized, dynamically guided oncology care. Future innovations, such as chromatin accessibility analysis and cfDNA fragmentation profiling, may further refine diagnostic precision and therapeutic monitoring.

Keywords

cancer diagnostics / DNA methylation / epigenetic markers / liquid biopsy / noncoding RNAs

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