Methylated Glutathione S-transferase 1 (mGSTP1) is a potential plasma free DNA epigenetic marker of prognosis and response to chemotherapy in castrate-resistant prostate cancer

Background: Glutathione S-transferase 1 (GSTP1) inactivation is associated with CpG island promoter hypermethylation in the majority of prostate cancers (PCs). This study assessed whether the level of circulating methylated GSTP1 (mGSTP1) in plasma DNA is associated with chemotherapy response and ov...

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Veröffentlicht in:	British journal of cancer 2014-10, Vol.111 (9), p.1802-1809
Hauptverfasser:	Mahon, K L, Qu, W, Devaney, J, Paul, C, Castillo, L, Wykes, R J, Chatfield, M D, Boyer, M J, Stockler, M R, Marx, G, Gurney, H, Mallesara, G, Molloy, P L, Horvath, L G, Clark, S J
Format:	Artikel
Sprache:	eng
Schlagworte:	692/53/2422 692/699/67/1059/99 692/699/67/589/466 Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Biomarkers, Tumor - blood Biomarkers, Tumor - genetics Biomedical and Life Sciences Biomedicine Cancer Research Cancer therapies Chemotherapy Clinical Trials, Phase I as Topic Clinical Trials, Phase II as Topic CpG Islands DNA Methylation DNA, Neoplasm - blood DNA, Neoplasm - genetics Drug Resistance Enzymes Epidemiology Epigenetics Epigenomics Follow-Up Studies Glutathione S-Transferase pi - blood Glutathione S-Transferase pi - genetics Hospitals Humans Male Medical prognosis Medical research Medical sciences Metastasis Middle Aged Molecular Diagnostics Molecular Medicine Multiple tumors. Solid tumors. Tumors in childhood (general aspects) Neoplasm Staging Neoplastic Cells, Circulating - drug effects Neoplastic Cells, Circulating - metabolism Neoplastic Cells, Circulating - pathology Nephrology. Urinary tract diseases Oncology Plasma Polymerase Chain Reaction Prognosis Promoter Regions, Genetic - genetics Prospective Studies Prostate cancer Prostatic Neoplasms, Castration-Resistant - blood Prostatic Neoplasms, Castration-Resistant - drug therapy Prostatic Neoplasms, Castration-Resistant - genetics Prostatic Neoplasms, Castration-Resistant - mortality Survival Rate Tumors Tumors of the urinary system Urinary tract. Prostate gland Validation Studies as Topic
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Zusammenfassung:	Background: Glutathione S-transferase 1 (GSTP1) inactivation is associated with CpG island promoter hypermethylation in the majority of prostate cancers (PCs). This study assessed whether the level of circulating methylated GSTP1 (mGSTP1) in plasma DNA is associated with chemotherapy response and overall survival (OS). Methods: Plasma samples were collected prospectively from a Phase I exploratory cohort of 75 men with castrate-resistant PC (CRPC) and a Phase II independent validation cohort ( n =51). mGSTP1 levels in free DNA were measured using a sensitive methylation-specific PCR assay. Results: The Phase I cohort identified that detectable baseline mGSTP1 DNA was associated with poorer OS (HR, 4.2 95% CI 2.1–8.2; P
ISSN:	0007-0920 1532-1827
DOI:	10.1038/bjc.2014.463