Dataset Information

A urine-based DNA methylation assay, ProCUrE, to identify clinically significant prostate cancer.

ABSTRACT:

Background

Prevention of unnecessary biopsies and overtreatment of indolent disease remains a challenge in the management of prostate cancer. Novel non-invasive tests that can identify clinically significant (intermediate-risk and high-risk) diseases are needed to improve risk stratification and monitoring of prostate cancer patients. Here, we investigated a panel of six DNA methylation biomarkers in urine samples collected post-digital rectal exam from patients undergoing prostate biopsy, for their utility to guide decision making for diagnostic biopsy and early detection of aggressive prostate cancer.

Results

We recruited 408 patients in risk categories ranging from benign to low-, intermediate-, and high-risk prostate cancer from three international cohorts. Patients were separated into 2/3 training and 1/3 validation cohorts. Methylation biomarkers were analyzed in post-digital rectal exam urinary sediment DNA by quantitative MethyLight assay and investigated for their association with any or aggressive prostate cancers. We developed a Prostate Cancer Urinary Epigenetic (ProCUrE) assay based on an optimal two-gene (HOXD3 and GSTP1) LASSO model, derived from methylation values in the training cohort, and assessed ProCUrE's diagnostic and prognostic ability for prostate cancer in both the training and validation cohorts. ProCUrE demonstrated improved prostate cancer diagnosis and identification of patients with clinically significant disease in both the training and validation cohorts. Using three different risk stratification criteria (Gleason score, D'Amico criteria, and CAPRA score), we found that the positive predictive value for ProCUrE was higher (59.4-78%) than prostate specific antigen (PSA) (38.2-72.1%) for all risk category comparisons. ProCUrE also demonstrated additive value to PSA in identifying GS ??7 PCa compared to PSA alone (DeLong's test p?= 0.039), as well as additive value to the PCPT risk calculator for identifying any PCa and GS ??7 PCa (DeLong's test p?=?0.011 and 0.022, respectively).

Conclusions

ProCUrE is a promising non-invasive urinary methylation assay for the early detection and prognostication of prostate cancer. ProCUrE has the potential to supplement PSA testing to identify patients with clinically significant prostate cancer.

SUBMITTER: Zhao F

PROVIDER: S-EPMC6260648 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

A urine-based DNA methylation assay, ProCUrE, to identify clinically significant prostate cancer.

Zhao Fang F Olkhov-Mitsel Ekaterina E Kamdar Shivani S Jeyapala Renu R Garcia Julia J Hurst Rachel R Hanna Marcelino Yazbek MY Mills Robert R Tuzova Alexandra V AV O'Reilly Eve E Kelly Sarah S Cooper Colin C Brewer Daniel D Perry Antoinette S AS Clark Jeremy J Fleshner Neil N Bapat Bharati B

Clinical epigenetics 20181123 1

<h4>Background</h4>Prevention of unnecessary biopsies and overtreatment of indolent disease remains a challenge in the management of prostate cancer. Novel non-invasive tests that can identify clinically significant (intermediate-risk and high-risk) diseases are needed to improve risk stratification and monitoring of prostate cancer patients. Here, we investigated a panel of six DNA methylation biomarkers in urine samples collected post-digital rectal exam from patients undergoing prostate biops ...[more]

PMID: 30470249

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Project description:BackgroundCombining targeted biopsy (TB) with systematic biopsy (SB) is currently recommended as the first-line biopsy method by the European Association of Urology (EAU) guidelines in patients diagnosed with prostate cancer (PCa) with an abnormal magnetic resonance imaging (MRI). The combined SB and TB indeed detected an additional number of patients with clinically significant prostate cancer (csPCa); however, it did so at the expense of a concomitant increase in biopsy cores. Our study aimed to evaluate if ipsilateral SB (ipsi-SB) + TB or contralateral SB (contra-SB) + TB could achieve almost equal csPCa detection rates as SB + TB using fewer cores based on a different csPCa definition.MethodsPatients with at least one positive prostate lesion were prospectively diagnosed by MRI. The combination of TB and SB was conducted in all patients. We compared the csPCa detection rates of the following four hypothetical biopsy sampling schemes with those of SB + TB: SB, TB, ipsi-SB + TB, and contra-SB + TB.ResultsThe study enrolled 279 men. The median core of SB, TB, ipsi-SB + TB, and contra-SB + TB was 10, 2, 7 and 7, respectively (P < 0.001). ipsi-SB + TB detected significantly more patients with csPCa than contra-SB + TB based on the EAU guidelines (P = 0.042). They were almost equal on the basis of the Epstein criteria (P = 1.000). Compared with SB + TB, each remaining method detected significantly fewer patients with csPCa regardless of the definition (P < 0.001) except ipsi-SB + TB on the grounds of D1 (P = 0.066). Ten additional subjects were identified with a higher Gleason score (GS) on contra-SB + TB, and only one was considered as significantly upgraded (GS = 6 on ipsi-SB + TB to a GS of 8 on contra-SB + TB).ConclusionsIpsi-SB + TB could acquire an almost equivalent csPCa detection value to SB + TB using significantly fewer cores when csPCa was defined according to the EAU guidelines. Given that there was only one significantly upgrading patient on contra-SB, our results suggested that contra-SB could be avoided.

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Dataset Information

A urine-based DNA methylation assay, ProCUrE, to identify clinically significant prostate cancer.

Background

Results

Conclusions

Publications

A urine-based DNA methylation assay, ProCUrE, to identify clinically significant prostate cancer.

Similar Datasets

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