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Epigenetic markers in circulating cell-free DNA as prognostic markers for survival of castration-resistant prostate cancer patients.
Hendriks, Rianne J; Dijkstra, Siebren; Smit, Frank P; Vandersmissen, Johan; Van de Voorde, Hendrik; Mulders, Peter F A; van Oort, Inge M; Van Criekinge, Wim; Schalken, Jack A.
Afiliación
  • Hendriks RJ; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Dijkstra S; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Smit FP; MDxHealth, Inc., Irvine, California.
  • Vandersmissen J; MDxHealth, Inc., Irvine, California.
  • Van de Voorde H; MDxHealth, Inc., Irvine, California.
  • Mulders PFA; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • van Oort IM; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Van Criekinge W; Department of Mathematical Modeling, Statistics and Bio-Informatics, Ghent University, Ghent, Belgium.
  • Schalken JA; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
Prostate ; 78(5): 336-342, 2018 04.
Article en En | MEDLINE | ID: mdl-29330943
BACKGROUND: Noninvasive biomarkers to guide personalized treatment for castration-resistant prostate cancer (CRPC) are needed. In this study, we analyzed hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA concentrations and levels of the epigenetic markers and to assess the value of these biomarkers for prognosis. METHODS: In this prospective study, patients were included before starting new treatment after developing CRPC. The blood samples were collected prior to start of the treatment and at three time points thereafter. cfDNA was extracted from 1.5 mL of plasma and before performing a methylation-specific PCR, bisulfate modification was carried out. RESULTS: The median levels of cfDNA, GSTP1, and APC copies in the baseline samples of CRPC patients (n = 47) were higher than in controls (n = 30). In the survival analysis, the group with baseline marker levels below median had significant less PCa-related deaths (P-values <0.02) and did not reach the median survival point. The survival distributions for the groups were statistically significant for the cfDNA concentration, GSTP1 and APC copies, as well as PSA combined with GSTP1 + APC (P-values <0.03). Furthermore, there were strong positive correlations between PSA and marker response after starting treatment (P-values <0.04). CONCLUSIONS: In conclusion, this study showed the kinetics of methylated cfDNA (GSTP1 and APC) in plasma of CRPC patients after starting treatment. Furthermore, the value of the markers before treatment is prognostic for overall survival. These results are promising for developing a test to guide treatment-decision-making for CRPC patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Resistentes a la Castración / Ácidos Nucleicos Libres de Células / ADN Tumoral Circulante Tipo de estudio: Observational_studies / Prognostic_studies Límite: Adult / Aged / Humans / Male / Middle aged Idioma: En Revista: Prostate Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata Resistentes a la Castración / Ácidos Nucleicos Libres de Células / ADN Tumoral Circulante Tipo de estudio: Observational_studies / Prognostic_studies Límite: Adult / Aged / Humans / Male / Middle aged Idioma: En Revista: Prostate Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Estados Unidos