An Epigenetic Signature is Associated with Serum 25‐Hydroxyvitamin D in Colorectal Cancer Tumors

Abstract

Introduction Vitamin D has been widely associated with colorectal cancer (CRC) through different insights. This study aims to explore the association between serum 25‐hydroxyvitamin D (25(OH)D) and the global DNA methylation in tumor from CRC patients. Methods and Results A genome‐wide DNA methylation analysis is conducted in 20 CRC patients under categorical (10 patients have 25(OH)D <30 ng mL−1; 10 patients with 25(OH)D ≥30 ng mL−1) and continuous models of 25(OH)D. A total of 95 differentially methylated CpGs (DMCpGs) are detected under the categorical model (false discovery rate (FDR) < 0.05), while 16 DMCpGs are found under the continuous model. Regional analysis showed eight vitamin D‐associated differentially methylated regions (DMR). Between them, a DMR is the most significant at cAMP‐Dependent Protein Kinase Inhibitor Alpha (PKIA) locus. Furthermore, seven genes, including PKIA gene, have more or equal than two significant DMCpGs. The protein networking analysis found pathways implicated in cell adhesion and extracellular matrix, as well as signaling transduction. Conclusions This study identifies novel epigenetic loci associated with serum 25(OH)D status. Interestingly, also, a positive association between vitamin D and DNA methylation in the CRC context is found, suggesting a role in CRC. Further studies are warranted to clarify and replicate these results.

Novel DNA methylation-based epigenetic signatures in colorectal cancer from peripheral blood leukocytes

“…Epigenetic mechanisms may address these issues. In fact, Am J Cancer Res 2024;14 (5):2253-2271 differential epigenetic patterns in CRC reflect interactions between environmental exposures and genetic influences, conferring cellular plasticity with specific cellular states, regulating gene expression, and consequently affecting cancer development [10][11][12][13][14][15]. Further, the epigenome influences accumulation of DNA mutations, controls important tumor cell phenotypes [16], and finally exerts a driving effect on CRC risk in the combined analyses of epigenetic alterations and genetic mutations [17], suggesting its crucial role during CRC development.…”