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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

Mahon, K. K., Qu, W., Devaney, J., Paul, C., Castillo, L., Wykes, R. J., Chatfield, Mark, Boyer, Michael J., Stockler, M. R., Marx, G., Gurney, H., Mallesara, G., Molloy, P. L., Horvath, L. G., Clark, S. J. and PRIMe consortium (2014). 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. British Journal of Cancer,111(9):1802-1809.

Document type: Journal Article
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IRMA ID 75039815xPUB308
Title 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
Author Mahon, K. K.
Qu, W.
Devaney, J.
Paul, C.
Castillo, L.
Wykes, R. J.
Chatfield, Mark
Boyer, Michael J.
Stockler, M. R.
Marx, G.
Gurney, H.
Mallesara, G.
Molloy, P. L.
Horvath, L. G.
Clark, S. J.
PRIMe consortium
Journal Name British Journal of Cancer
Publication Date 2014
Volume Number 111
Issue Number 9
ISSN 0007-0920   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84908548256
Start Page 1802
End Page 1809
Total Pages 8
Place of Publication United Kingdom
Publisher Nature Publishing Group
HERDC Category C1 - Journal Article (DIISR)
Abstract 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<0.0001). A decrease in mGSTP1 DNA levels after cycle 1 was associated with a PSA response (P=0.008). In the Phase II cohort, baseline mGSTP1 DNA was a stronger predictor of OS than PSA change after 3 months (P=0.02). Undetectable plasma mGSTP1 after one cycle of chemotherapy was associated with PSA response (P=0.007).
Conclusions:
We identified plasma mGSTP1 DNA as a potential prognostic marker in men with CRPC as well as a potential surrogate therapeutic efficacy marker for chemotherapy and corroborated these findings in an independent Phase II cohort. Prospective Phase III assessment of mGSTP1 levels in plasma DNA is now warranted.
DOI http://dx.doi.org/10.1038/bjc.2014.463   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Description for Link Link to publisher's version
URL http://www.nature.com/bjc/journal/v111/n9/full/bjc2014463a.html
 
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Created: Wed, 19 Aug 2015, 12:15:28 CST