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Urinary DNA Methylation Biomarkers for Noninvasive Prediction of Aggressive Disease in Patients with Prostate Cancer on Active Surveillance
- Source :
- Journal of Urology. 197:335-341
- Publication Year :
- 2017
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2017.
-
Abstract
- Patients with prostate cancer on active surveillance are monitored by repeat prostate specific antigen measurements, digital rectal examinations and prostate biopsies. A subset of patients on active surveillance will later reclassify with disease progression, prompting definitive treatment. To minimize the risk of under treating such patients on active surveillance minimally invasive tests are urgently needed incorporating biomarkers to identify patients who will reclassify.We assessed post-digital rectal examination urine samples of patients on active surveillance for select DNA methylation biomarkers that were previously investigated in radical prostatectomy specimens and shown to correlate with an increasing risk of prostate cancer. Post-digital rectal examination urine samples were prospectively collected from 153 men on active surveillance who were diagnosed with Gleason score 6 disease. Urinary sediment DNA was analyzed for 8 DNA methylation biomarkers by multiplex MethyLight assay. Correlative analyses were performed on gene methylation and clinicopathological variables to test the ability to predict patient risk reclassification.Using backward logistic regression a 4-gene methylation classifier panel (APC, CRIP3, GSTP1 and HOXD8) was identified. The classifier panel was able to predict patient reclassification (OR 2.559, 95% CI 1.257-5.212). We observed this panel to be an independent and superior predictor compared to current clinical predictors such as prostate specific antigen at diagnosis or the percent of tumor positive cores in the initial biopsy.We report that a urine based classifier panel of 4 methylation biomarkers predicts disease progression in patients on active surveillance. Once validated in independent active surveillance cohorts, these promising biomarkers may help establish a less invasive method to monitor patients on active surveillance programs.
- Subjects :
- Adult
Male
0301 basic medicine
Oncology
medicine.medical_specialty
Pathology
Urology
medicine.medical_treatment
Urinary system
Disease
Risk Assessment
03 medical and health sciences
Prostate cancer
0302 clinical medicine
Predictive Value of Tests
Prostate
Internal medicine
Biomarkers, Tumor
medicine
Humans
Prospective Studies
Aged
Digital Rectal Examination
Aged, 80 and over
medicine.diagnostic_test
business.industry
Prostatectomy
Prostatic Neoplasms
Rectal examination
DNA Methylation
Middle Aged
medicine.disease
Prostate-specific antigen
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
DNA methylation
Disease Progression
Neoplasm Grading
business
Multiplex Polymerase Chain Reaction
Subjects
Details
- ISSN :
- 15273792 and 00225347
- Volume :
- 197
- Database :
- OpenAIRE
- Journal :
- Journal of Urology
- Accession number :
- edsair.doi.dedup.....c225276476aecf003dbf9e16b1ecd1cf