Clinical Significance of Measuring Global Hydroxymethylation of White Blood Cell DNA in Prostate Cancer: Comparison to PSA in a Pilot Exploratory Study

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.

DNA Methylation and Hydroxymethylation in Cervical Cancer: Diagnosis, Prognosis and Treatment

“…Owing to the loss of hydroxymethylation, different cancers maintain low levels of 5-hmC (Feng et al, 2015;Strand et al, 2015;Kamdar et al, 2016;Spans et al, 2016). However, Grelus et al (2017) have shown that hydroxymethylation markers cannot be single biomarkers for PCa diagnosis. They should be used as a supplement for prostate-specific antigen to diagnose PCa.…”

“…They should be used as a supplement for prostate-specific antigen to diagnose PCa. Although hydroxymethylation can be detected in multiple cancer types, the utility of genomic hydroxymethylation in diagnosing cancer may only be restricted to one type of cancer (Grelus et al, 2017). Thus, whether DNA hydroxymethylation can be used in clinical diagnosis needs to be explored.…”

Serum YKL-40 Levels in Patients with Asthma or COPD: A Pilot Study

“…The homogeneity of Caucasian patients diagnosed with BA or COPD in terms of age and sex was analyzed using a Mann–Whitney U test and a Chi-square (χ 2 ) test, respectively [ 23 ]. The χ 2 tests were next applied to determine inter-group differences in the distribution of subjects stratified based on the area of origin (urban vs. rural) and current status of smoking (non-smoker vs. smoker).…”

DNA hydroxymethylation combined with carotid plaques as a novel biomarker for coronary atherosclerosis

“…Genomic DNA methylation and hydroxymethylation were determined by measuring 5-mC and 5-hmC using 5-mC DNA ELISA Kit and Quest 5-hmC TM DNA ELISA Kit (Zymo Research, Irvine, CA, USA), respectively [46, 47]. These are the most cited ELISA-based global 5-mC and 5-hmC quantification kit in the literature, and provides scientists with a quick, cost-effective and reliable alternative to chromatographic methods [48, 49]. Assays were performed according to the manufacturer’s instructions loading 100 ng of DNA per well.…”