Integrated Molecular, Epigenetic, Microbial, and Liquid Biopsy Biomarkers in Colorectal Cancer: Implications for Prognosis and Precision Therapy

BackgroundColorectal cancer (CRC) is a biologically diverse malignancy driven by a complex interplay of genetic mutations, epigenetic changes, tumour microenvironmental factors, and host-microbial interactions. Foundational molecular events including APC-associated Wnt/β-catenin dysregulation, TP53 inactivation, KRAS and BRAF mutations, and aberrant PI3K/AKT signalling due to PIK3CA and PTEN alterations, contribute significantly to disease initiation, progression, and therapeutic resistance. Microsatellite instability (MSI), arising from defective DNA mismatch repair, defines a distinct subset of CRC with characteristic biological and therapeutic behaviour.ObjectiveThis review critically evaluates established and emerging molecular biomarkers for CRC, highlighting their mechanistic significance and translational relevance in the evolving precision oncology landscape.MethodsA comprehensive narrative evaluation of the literature was conducted, focusing on pathways regulating oncogenes, regulatory microRNAs, gut microbiota dysbiosis, and liquid biopsy approaches, particularly circulating tumour cells (CTCs) and circulating free DNA (cfDNA).ResultsCore molecular alterations remain central to CRC pathogenesis and influence treatment responsiveness. Increasing evidence also supports the role of microRNA dysregulation and microbiome imbalance in modulating tumour progression and immune escape. Liquid biopsy technologies offer minimally invasive, real-time assessment of tumour development.DiscussionAn integrated understanding of molecular drivers and emerging biomarker platforms is essential for advancing personalised CRC management.