RGD Reference Report - Effect of DNA Methylation on Identification of Aggressive Prostate Cancer. - Rat Genome Database

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Effect of DNA Methylation on Identification of Aggressive Prostate Cancer.

Authors: Alumkal, JJ  Zhang, Z  Humphreys, EB  Bennett, C  Mangold, LA  Carducci, MA  Partin, AW  Garrett-Mayer, E  Demarzo, AM  Herman, JG 
Citation: Alumkal JJ, etal., Urology. 2008 Apr 1;.
RGD ID: 2293539
Pubmed: PMID:18387661   (View Abstract at PubMed)
PMCID: PMC2874954   (View Article at PubMed Central)
DOI: DOI:10.1016/j.urology.2007.12.060   (Journal Full-text)

OBJECTIVES: Biochemical (prostate-specific antigen) recurrence of prostate cancer after radical prostatectomy remains a major problem. Better biomarkers are needed to identify high-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the effect of DNA methylation on the identification of recurrent prostate cancer. METHODS: We studied the methylation status of 15 pre-specified genes using methylation-specific polymerase chain reaction on tissue samples from 151 patients with localized prostate cancer and at least 5 years of follow-up after prostatectomy. RESULTS: On multivariate logistic regression analysis, a high Gleason score and involvement of the capsule, lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of biochemical recurrence. Methylation of CDH13 by itself (odds ratio 5.50, 95% confidence interval [CI] 1.34 to 22.67; P = 0.02) or combined with methylation of ASC (odds ratio 5.64, 95% CI 1.47 to 21.7; P = 0.01) was also associated with an increased risk of biochemical recurrence. The presence of methylation of ASC and/or CDH13 yielded a sensitivity of 72.3% (95% CI 57% to 84.4%) and negative predictive value of 79% (95% CI 66.8% to 88.3%), similar to the weighted risk of recurrence (determined from the lymph node status, seminal vesicle status, surgical margin status, and postoperative Gleason score), a powerful clinicopathologic prognostic score. However, 34% (95% CI 21% to 49%) of the patients with recurrence were identified by the methylation profile of ASC and CDH13 rather than the weighted risk of recurrence. CONCLUSIONS: The results of our study have shown that methylation of CDH13 alone or combined with methylation of ASC is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even considering the weighted risk of recurrence score. These findings should be validated in an independent, larger cohort of patients with prostate cancer who have undergone radical prostatectomy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate cancer disease_progressionIDA 2293539DNA:hypermethylation:promoterRGD 
prostate cancer disease_progressionISOCDH13 (Homo sapiens)2293539; 2293539DNA:hypermethylation:promoterRGD 

Objects Annotated

Genes (Rattus norvegicus)
Cdh13  (cadherin 13)

Genes (Mus musculus)
Cdh13  (cadherin 13)

Genes (Homo sapiens)
CDH13  (cadherin 13)


Additional Information