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DNA Methylation Scr...
DNA Methylation Screening of Primary Prostate Tumors Identifies SRD5A2 and CYP11A1 as Candidate Markers for Assessing Risk of Biochemical Recurrence
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- Horning, A. M. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Awe, Julius Adebayo (author)
- Högskolan i Skövde,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik,Institute of Biomedicine, Department of Medical and Clinical Genetics,Institutionen för biovetenskap,Forskningscentrum för Systembiologi,Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada / Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden,Tumörbiologi, Tumor Biology
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- Wang, C. M. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Liu, J. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Lai, Z. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Wang, V. Y. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Jadhav, R. R. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Louie, A. D. (author)
- University of Texas Health Science Center, San Antonio, USA,University of Manitoba, Winnipeg, Canada
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- Lin, C. L. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Kroczak, T. (author)
- University of Manitoba, Winnipeg, Manitoba, Canada
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- Chen, Y. D. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Jin, V. X. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Abboud-Werner, S. L. (author)
- University of Texas Health Science Center, San Antonio, USA
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Leach, R. J. (author)
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- Hernandez, J. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Thompson, I. M. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Saranchuk, J. (author)
- University of Manitoba, Winnipeg, Canada
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Drachenberg, D. (author)
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- Chen, C. L. (author)
- University of Texas Health Science Center, San Antonio, USA
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- Mai, S. (author)
- University of Manitoba, Winnipeg, Canada
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- Huang, T. H. M. (author)
- University of Texas Health Science Center, San Antonio, USA
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(creator_code:org_t)
- 2015-09-01
- 2015
- English.
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In: Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 75:15, s. 1790-1801
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- BACKGROUND. Altered DNA methylation in CpG islands of gene promoters has been implicated in prostate cancer (PCa) progression and can be used to predict disease outcome. In this study, we determine whether methylation changes of androgen biosynthesis pathway (ABP)-related genes in patients' plasma cell-free DNA (cfDNA) can serve as prognostic markers for biochemical recurrence (BCR). METHODS. Methyl-binding domain capture sequencing (MBDCap-seq) was used to identify differentially methylated regions (DMRs) in primary tumors of patients who subsequently developed BCR or not, respectively. Methylation pyrosequencing of candidate loci was validated in cfDNA samples of 86 PCa patients taken at and/or post-radical prostatectomy (RP) using univariate and multivariate prediction analyses. RESULTS. Putative DMRs in 13 of 30 ABP-related genes were found between tumors of BCR (n = 12) versus no evidence of disease (NED) (n = 15). In silico analysis of The Cancer Genome Atlas data confirmed increased DNA methylation of two loci-SRD5A2 and CYP11A1, which also correlated with their decreased expression, in tumors with subsequent BCR development. Their aberrant cfDNA methylation was also associated with detectable levels of PSA taken after patients' post-RP. Multivariate analysis of the change in cfDNA methylation at all of CpG sites measured along with patient's treatment history predicted if a patient will develop BCR with 77.5% overall accuracy. CONCLUSIONS. Overall, increased DNA methylation of SRD5A2 and CYP11A1 related to androgen biosynthesis functions may play a role in BCR after patients' RP. The correlation between aberrant cfDNA methylation and detectable PSA in post-RP further suggests their utility as predictive markers for PCa recurrence. (C) 2015 Wiley Periodicals, Inc.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- prostate cancer
- DNA methylation
- plasma
- biochemical recurrence
- GENE-EXPRESSION
- RADICAL PROSTATECTOMY
- CANCER PROGRESSION
- CIRCULATING
- DNA
- ANTIGEN
- PLASMA
- GROWTH
- SERUM
- TESTOSTERONE
- FINASTERIDE
- Endocrinology & Metabolism
- Urology & Nephrology
- ATES OF AMERICA
- V108
- P13728
- prostate cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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Prostate
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- By the author/editor
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Horning, A. M.
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Awe, Julius Adeb ...
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Wang, C. M.
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Liu, J.
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Lai, Z.
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Wang, V. Y.
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show more...
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Jadhav, R. R.
-
Louie, A. D.
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Lin, C. L.
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Kroczak, T.
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Chen, Y. D.
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Jin, V. X.
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Abboud-Werner, S ...
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Leach, R. J.
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Hernandez, J.
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Thompson, I. M.
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Saranchuk, J.
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Drachenberg, D.
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Chen, C. L.
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Mai, S.
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Huang, T. H. M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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and Basic Medicine
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and Medical Genetics
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Prostate
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University of Gothenburg
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University of Skövde