DNA Methylation in Autophagy-associated Genes and Risk of Prostate Cancer

The study of autophagy is a growing field that is emerging as one of the most important studies in cancer due to the nature of autophagy’s significant biological functions. The complex relationship between autophagy and prostate cancer is still under debate, with studies demonstrating inconsistent results in terms of tumor growth. DNA methylation is one of the key dynamic epigenetic mechanisms in gene regulation. This prospective study aims to understand the role of DNA methylation in autophagy-related genes and prostate cancer development. Among over 740 human autophagy-related genes we examined, 10 methylation biomarkers in the promoter regions of 12 genes, including 6 novel genes and 6 well-known genes, were found to be predictive to inform risk of prostate cancer at least 4 years before cancer diagnosis. Pathways analysis revealed that these genes involved in necroptosis and calcium signaling, which play key roles in autophagy and prostate cancer development. Within 4 years pre-diagnosis, the relationships between methylation of these genes and cancer development became obscure and insignificant, which indicate an accumulation of epigenetic “noise” in advancing malignant disease that confounds the methylation biomarkers and thus may explain prior inconsistent studies. Our study suggests that methylation in autophagy-related genes may serve as novel therapeutic biomarkers for further study