Abstract
This is the first study investigating the clinical relevance of 5-hydroxymethylcytosine (5hmC) in genomic DNA from white blood cells (WBC) in the context of prostate cancer (PCa) and other prostate pathologies. Using an enzyme-linked immunosorbent assay, we identified significantly different distributions of patients with low and elevated 5hmC content in WBC DNA across controls and patients with prostate cancer (PCa), atypical small acinar proliferation (ASAP), and benign prostatic hyperplasia (BPH). The measured values were within the normal range for most PCa patients, while the latter category was predominant for ASAP. We observed a wider heterogeneity in 5hmC content in all of the prostate pathologies analyzed when compared to the healthy age-matched controls. When compared to blood levels of prostate-specific antigen (PSA), this 5hmC-based biomarker had a lower performance in PCa detection than the use of a PSA cut-off of 2.5 nanograms per milliliter (ng/mL). Above this threshold, however, it delineated almost three quarters of PCa patients from controls and patients with other prostate pathologies. Overall, genome-wide 5hmC content of WBC DNA appears to be applicable for detecting non-cancerous prostate diseases, rather than PCa. Our results also suggest a potential clinical usefulness of complementing PSA as a PCa marker by the addition of a set of hydroxymethylation markers in the blood, but further studies are necessary to confirm these findings.
Highlights
The incidence of prostate diseases is expected to substantially increase during the decades as the world’s ageing population continues to grow
The median values of the blood prostate-specific antigen (PSA) levels tended to increase with the severity of prostate pathology (Table 1), with the prostate cancer (PCa) patients displaying the widest interquartile range (IQR)
We investigated for the first time the potential clinical significance of 5-hydroxymethylcytosine in genomic DNA from white blood cells in the context of disturbed prostatic function
Summary
The incidence of prostate diseases is expected to substantially increase during the decades as the world’s ageing population continues to grow. Convincing evidence supports that about two-thirds of PSA results are false-positives for PCa [4,5,6], which may lead to overdiagnosis, overtreatment, and adverse effects that the treatment may cause [7] In this context, much emphasis has been put on developing and validating novel molecular biomarkers for PCa detection and prognosis. Leukocytes) for this purpose [18] This source of DNA provides investigators with a rich source of quality DNA, which is readily obtainable via non-invasive methods and is easy handleable for laboratory processing and clinical use [19]. Despite these advantages, no studies have examined the 5hmC content of WBC DNA in connection with PCa or any other prostate pathology type
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