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Using the epigenetic field defect to detect prostate cancer in biopsy negative patients.
Truong, Matthew; Yang, Bing; Livermore, Andrew; Wagner, Jennifer; Weeratunga, Puspha; Huang, Wei; Dhir, Rajiv; Nelson, Joel; Lin, Daniel W; Jarrard, David F.
Afiliação
  • Truong M; University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
J Urol ; 189(6): 2335-41, 2013 Jun.
Article em En | MEDLINE | ID: mdl-23159584
PURPOSE: We determined whether a novel combination of field defect DNA methylation markers could predict the presence of prostate cancer using histologically normal transrectal ultrasound guided biopsy cores. MATERIALS AND METHODS: Methylation was assessed using quantitative Pyrosequencing® in a training set consisting of 65 nontumor and tumor associated prostate tissues from University of Wisconsin. A multiplex model was generated using multivariate logistic regression and externally validated in blinded fashion in a set of 47 nontumor and tumor associated biopsy specimens from University of Washington. RESULTS: We observed robust methylation differences in all genes at all CpGs assayed (p <0.0001). Regression models incorporating individual genes (EVX1, CAV1 and FGF1) and a gene combination (EVX1 and FGF1) discriminated nontumor from tumor associated tissues in the original training set (AUC 0.796-0.898, p <0.001). On external validation uniplex models incorporating EVX1, CAV1 or FGF1 discriminated tumor from nontumor associated biopsy negative specimens (AUC 0.702, 0.696 and 0.658, respectively, p <0.05). A multiplex model (EVX1 and FGF1) identified patients with prostate cancer (AUC 0.774, p = 0.001) and had a negative predictive value of 0.909. Comparison between 2 separate cores in patients in this validation set revealed similar methylation defects, indicating detection of a widespread field defect. CONCLUSIONS: A widespread epigenetic field defect can be used to detect prostate cancer in patients with histologically negative biopsies. To our knowledge this assay is unique, in that it detects alterations in nontumor cells. With further validation this marker combination (EVX1 and FGF1) has the potential to decrease the need for repeat prostate biopsies, a procedure associated with cost and complications.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Fator 1 de Crescimento de Fibroblastos / Proteínas de Homeodomínio / Metilação de DNA / Epigenômica Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Humans / Male / Middle aged Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Fator 1 de Crescimento de Fibroblastos / Proteínas de Homeodomínio / Metilação de DNA / Epigenômica Tipo de estudo: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Aged / Aged80 / Humans / Male / Middle aged Idioma: En Ano de publicação: 2013 Tipo de documento: Article