Unraveling TNXB Epigenetic Alterations through Genome wide DNA methylation and their Implications for Colorectal Cancer Pathogenesis

Background: Aberrant DNA methylation has been shown to be a fingerprint charac-teristic in human colorectal tumors. In this study, we hypothesize that investigating global DNA methylation could offer potential candidates for clinical application in CRC. The epigenome-wide association analysis was conducted using in tumor area (N=27) and the adjacent tumor-free (NAT) area (N=15). Results. We found 78,935 differentially methylated CpG sites (DMCs) (FDR< 0.05), 42,888 hypomethylated and 36,047 hyper-methylation showing overall hypomethylation. Gene Ontology and KEGG analysis of genes differentially methylated genes showed a significant enrichment of develop-mental genes, such as and metabolic process and cell cycle, such as TFGβ and cAMP signaling pathways. Through filtered analysis, we identified TNXB gene as the most epigenetically dysregulated gene, in which it found to be hypomethylated and down-regulated in CRC (both with p< 0.001) after further validation and associated with poor overall survival. In the functional analysis, TNXB was epigenetically regulated, in dose-dependent manner, suggesting a potential role in CRC. Conclusion. The epigenetic dysregulation and functional role of TNXB in CRC could have clinical implications, serving as an indicator of malignant potential and the adverse effects associated with disease origin and progression in CRC