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Validation of an epigenetic field of susceptibility to detect significant prostate cancer from non-tumor biopsies.
- Source :
-
Clinical epigenetics [Clin Epigenetics] 2019 Nov 28; Vol. 11 (1), pp. 168. Date of Electronic Publication: 2019 Nov 28. - Publication Year :
- 2019
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Abstract
- Background: An epigenetic field of cancer susceptibility exists for prostate cancer (PC) that gives rise to multifocal disease in the peripheral prostate. In previous work, genome-wide DNA methylation profiling identified altered regions in the normal prostate tissue of men with PC. In the current multicenter study, we examined the predictive strength of a panel of loci to detect cancer presence and grade in patients with negative biopsy tissue.<br />Results: Four centers contributed benign prostate biopsy tissues blocks from 129 subjects that were either tumor associated (TA, Grade Group [GG] ≥ 2, n = 77) or non-tumor associated (NTA, n = 52). Biopsies were analyzed using pyrosequencing for DNA methylation encompassing CpG loci near CAV1, EVX1, FGF1, NCR2, PLA2G16, and SPAG4 and methylation differences were detected within all gene regions (p < 0.05). A multiplex regression model for biomarker performance incorporating a gene combination discriminated TA from NTA tissues (area under the curve [AUC] 0.747, p = 0.004). A multiplex model incorporating all the above genes and clinical information (PSA, age) identified patients with GG ≥ 2 PC (AUC 0.815, p < 0.0001). In patients with cancer, increased variation in gene methylation levels occurs between biopsies across the prostate.<br />Conclusions: A widespread epigenetic field defect is utilized to detect GG ≥ 2 PC in patients with histologically negative biopsies. These alterations in non-tumor cells display increased heterogeneity of methylation extent and are spatially distant from tumor foci. These findings have the potential to decrease the need for repeated prostate biopsy.
Details
- Language :
- English
- ISSN :
- 1868-7083
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- 31779677
- Full Text :
- https://doi.org/10.1186/s13148-019-0771-5