Personalized Medicine in Idiopathic Pulmonary Fibrosis
Three major types of epigenetic markers have been associated with lung fibrogenesis including DNA methylation, histone modifications and noncoding RNAs. Genome-wide methylation arrays have been applied in a small cohort of 12 patients with IPF, and revealed that an intermediate DNA methylation profile between lung cancer and control individuals was present in patients with IPF. High-throughput methylation and gene expression arrays have been recently used in a cohort of 100 IPF patients and demonstrated that TOLLIP and NOTCH1 were among the most differentially methylated and expressed genes, between patients and controls. An accumulating body of evidence has also implicated microRNAs as major regulators of fibrogenesis through silencing of several profibrotic or antifibrotic target genes. Among the most downregulated and so-called 'protective' miRNAs, in patients with IPF compared to controls, were let-7d and miR-29, whereas miR-21 and miR-154 were found to be upregulated. Despite useful pathogenetic insights, there has been only one study investigating the role of miRNAs as disease prognosticators. A panel of miRNAs (miR-302c, miR-423, miR-210, miR-376c and miR-185) in lung biopsies from patients with IPF has been shown to differentiate rapid from slow progressors.
Epigenetic Markers
Three major types of epigenetic markers have been associated with lung fibrogenesis including DNA methylation, histone modifications and noncoding RNAs. Genome-wide methylation arrays have been applied in a small cohort of 12 patients with IPF, and revealed that an intermediate DNA methylation profile between lung cancer and control individuals was present in patients with IPF. High-throughput methylation and gene expression arrays have been recently used in a cohort of 100 IPF patients and demonstrated that TOLLIP and NOTCH1 were among the most differentially methylated and expressed genes, between patients and controls. An accumulating body of evidence has also implicated microRNAs as major regulators of fibrogenesis through silencing of several profibrotic or antifibrotic target genes. Among the most downregulated and so-called 'protective' miRNAs, in patients with IPF compared to controls, were let-7d and miR-29, whereas miR-21 and miR-154 were found to be upregulated. Despite useful pathogenetic insights, there has been only one study investigating the role of miRNAs as disease prognosticators. A panel of miRNAs (miR-302c, miR-423, miR-210, miR-376c and miR-185) in lung biopsies from patients with IPF has been shown to differentiate rapid from slow progressors.
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