Evaluation of the clinical value of the newly identified urine biomarker HIST1H4K for diagnosis and prognosis of prostate cancer in Bulgarian patients.
OBJECTIVE
Searching for diagnostic and prognostic biomarkers for prostate cancer (PC) is main public health priority. DNA methylation in body fluids is a stable, easily detectable and promising PC biomarker. The major advantages of urine-based assays are their noninvasive nature and the ability to monitor PC with heterogeneous foci. The aim of this study was to determine the diagnostic value of the recently identified candidate PC biomarker HIST1H4K.


METHODS
We investigated DNA methylation of HIST1H4K in urine samples from 57 PC patients, 29 controls with benign prostatic hyperplasia (BPH) and 50 young asymptomatic men (YAM) by MethyLight real-time PCR.


RESULTS
The frequency of HIST1H4K promoter hypermethylation significantly discriminated PC patients from YAM (AUC =0.763; 95% CI 0.672-0.839; p<0.0001), but did not show any statistical difference between PC patients and BPH controls (AUC=0.513, 95% CI 0.402-0.622; p=0.8255). HIST1H4K could not outperform the prostatic specific antigen (PSA) in our sample (AUC=0.785; 95% CI 0.679-0.870; p<0.0001). Methylation of HIST1H4K showed significant correlation with aging (r=0.5418; p<0.0001), but with no other clinicopathological characteristics.


CONCLUSIONS
The results suggest that the promoter hypermethylation of HIST1H4K is rather due to aging than related to prostate carcinogenesis. To elucidate this observation analysis of larger samples is needed.
Department of Medical Chemistry and Biochemistry and Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria.
D
D
Kachakova
A
A
Mitkova
E
E
Popov
O
O
Beltcheva
A
A
Vlahova
T
T
Dikov
S
S
Hristova
V
V
Mitev
C
C
Slavov
R
R
Kaneva
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D016022:Case-Control Studies; D019175:DNA Methylation; D005500:Follow-Up Studies; D006657:Histones / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017430:Prostate-Specific Antigen / Q000097:blood; D011470:Prostatic Hyperplasia / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
D014408:Biomarkers, Tumor; D006657:Histones; D017430:Prostate-Specific Antigen