Premium
A DNA hypermethylation profile reveals new potential biomarkers for prostate cancer diagnosis and prognosis
Author(s) -
Ashour Nadia,
Angulo Javier C.,
Andrés Guillermo,
Alelú Raúl,
GonzálezCorpas Ana,
Toledo María V.,
RodríguezBarbero José M.,
López Jose I.,
SánchezChapado Manuel,
Ropero Santiago
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22833
Subject(s) - prostate cancer , dna methylation , pca3 , cancer , biomarker , medicine , oncology , epigenetics , prostate , methylation , population , cancer research , gene , biology , genetics , gene expression , environmental health
BACKGROUND DNA hypermethylation has emerged as a novel molecular biomarker for the evaluation of prostate cancer diagnosis and prognosis. Defining the specific gene hypermethylation profile for prostate cancer could involve groups of genes that specifically discriminate patients with indolent and aggressive tumors. METHODS Genome‐wide methylation analysis was performed on 83 tumor and 10 normal prostate samples using the GoldenGate Methylation Cancer Panel I (Illumina, Inc.). All clinical stages of disease were considered. RESULTS We found 41 genes hypermethylated in more than 20% of the tumors analyzed ( P < 0.01). Of these, we newly identified GSTM2 and PENK as being genes that are hypermethylated in prostate cancer and that were simultaneously methylated in 40.9% of the tumors analyzed. We also identified panels of genes that are more frequently methylated in tumor samples with clinico‐pathological indicators of poor prognosis: a high Gleason score, elevated Ki‐67, and advanced disease. Of these, we found simultaneous hypermethylation of CFTR and HTR1B to be common in patients with a high Gleason score and high Ki‐67 levels; this might indicate the population at higher risk of therapeutic failure. The DNA hypermethylation profile was associated with cancer‐specific mortality (log‐rank test, P = 0.007) and biochemical recurrence‐free survival (log‐rank test, P = 0.0008). CONCLUSIONS Our findings strongly indicate that epigenetic silencing of GSTM2 and PENK is a common event in prostate cancer that could be used as a molecular marker for prostate cancer diagnosis. In addition, simultaneous HTR1B and CFTR hypermethylation could help discriminate aggressive from indolent prostate tumors. Prostate 74:1171–1182, 2014 . © 2014 Wiley Periodicals, Inc.