Aberrant DOCK2 , GRASP , HIF3A and PKFP Hypermethylation has Potential as a Prognostic Biomarker for Prostate Cancer

• Published in: International journal of molecular sciences Vol. 20; no. 5; p. 1173
• Main Authors: Bjerre, Marianne T, Strand, Siri H, Nørgaard, Maibritt, Kristensen, Helle, Rasmussen, Anne Ki, Mortensen, Martin Mørck, Fredsøe, Jacob, Mouritzen, Peter, Ulhøi, Benedicte, Ørntoft, Torben, Borre, Michael, Sørensen, Karina D
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.03.2019; MDPI
• Subjects: Aged; Aged, 80 and over; Apoptosis Regulatory Proteins; Basic Helix-Loop-Helix Transcription Factors - genetics; Bioinformatics; biomarker; Biomarkers; Biomarkers, Tumor - genetics; Blood; Blood cells; Candidates; Carrier Proteins - genetics; Deoxyribonucleic acid; diagnosis; Diagnostic systems; DNA; DNA Methylation; Epigenesis, Genetic; epigenetics; GTPase-Activating Proteins; Guanine Nucleotide Exchange Factors - genetics; Humans; Hyperplasia; Kaplan-Meier Estimate; Male; Membrane Proteins - genetics; Middle Aged; Peripheral blood; Phosphofructokinase-1, Type C - genetics; Prognosis; Promoter Regions, Genetic; Prostate cancer; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Repressor Proteins; Sensitivity and Specificity; Survival Analysis; DNA methylation; diagnosis; prostate cancer; biomarker; prognosis; epigenetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20051173

Prostate cancer (PCa) is a clinically heterogeneous disease and currently, accurate diagnostic and prognostic molecular biomarkers are lacking. This study aimed to identify novel DNA hypermethylation markers for PCa with future potential for blood-based testing. Accordingly, to search for genes specifically hypermethylated in PCa tissue samples and not in blood cells or other cancer tissue types, we performed a systematic analysis of genome-wide DNA methylation data (Infinium 450K array) available in the Marmal-aid database for 4072 malignant/normal tissue samples of various types. We identified eight top candidate markers (cg12799885, , , , , , , and ) that were specifically hypermethylated in PCa tissue samples and hypomethylated in other benign and malignant tissue types, including in peripheral blood cells. Potential as diagnostic and prognostic biomarkers was further assessed by the quantitative methylation specific PCR (qMSP) analysis of 37 nonmalignant and 197 PCa tissue samples from an independent population. Here, all eight hypermethylated candidates showed high sensitivity (75⁻94%) and specificity (84⁻100%) for PCa. Furthermore, , , and hypermethylation was significantly associated with biochemical recurrence (BCR) after radical prostatectomy (RP; 197 patients), independent of the routine clinicopathological variables. is the most promising single candidate marker (hazard ratio (HR) (95% confidence interval (CI)): 1.96 (1.24⁻3.10), adjusted = 0.016; multivariate cox regression). Further validation studies are warranted and should investigate the potential value of these hypermethylation candidate markers for blood-based testing also.