Can epigenetic and inflammatory biomarkers identify clinically aggressive prostate cancer?

摘要

Prostate cancer(PCa)is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality.It emerges through the acquisition of genetic and epigenetic alterations.Epigenetic modifications include DNA methylation,histone modifications and micro RNA deregulation.These generate heritable transformations in the expression of genes but do not change the DNA sequence.Alterations in DNA methylation(hypo and hypermethylation)are the most characterized in PCa.They lead to genomic instability and inadequate gene expression.Major and minor-specific modifications in chromatin recasting are involved in PCa,with signs suggesting a dysfunction of enzymes modified by histones.Micro RNA deregulation also contributes to the initiation of PCa,including involvement in androgen receptor signalization and apoptosis.The influence of inflammation on prostate tumor carcinogenesis is currently much better known.Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation,promoting prostate inflammatory atrophy and eventually leading to PCa.Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa.The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis,treatment decisions,evaluation of prognosis and posttreatment surveillance.