A DNA hypermethylation profile reveals new potential biomarkers for prostate cancer diagnosis and prognosis

ABSTRACT: Detection of DNA hypermethylation has emerged as a novel molecular biomarker for the evaluation of prostate cancer diagnosis and prognosis, but the use of single gene hypermethylation could produce unspecific results. Defining the specific gene hypermethylation profile for prostate cancer could provide groups of genes that specifically discriminate the patients with indolent and aggressive tumors. To compare the methylation profile of normal and malignant prostate we performed Genome-wide methylation analysis on 83 tumor samples, that included all clinical stages of the disease, 10 normal prostate samples and LNCaP, DU145 and PC3 prostate cancer cell lines using the GoldenGate Methylation Cancer Panel I (Illumina, Inc.) that interrogate for 1505 CpGs. We found 41 genes significantly hypermethylated in more than 20% of the tumors analyzed (p<0.01). Of these we identified GSTM2 and PENK as novel hypermethylated genes in prostate cancer that were simultaneously methylated in 40.9% of the tumors analyzed. We also identified panels of genes more frequently methylated in tumor samples with clinico-pathological indicators of poor prognosis: high Gleason score, elevated Ki-67 or advanced disease. Of these, we found that simultaneous hypermethylation of CFTR and HTR1B is common in patients with high Gleason score and high ki-67 levels and might signal the population at higher risk of therapeutic failure. DNA hypermethylation profile was associated with cancer-specific mortality (log-rank, p=0.007) and biochemical recurrence-free survival (log-rank, p=0.0008). In conclusion, our data 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.A DNA hypermethylation profile associated with cancer-specific mortality and biochemical recurrence in patients receiving radical prostatectomy is presented. GST2 and PENK are new hipermethylated genes identified. Simultaneous hypermethylation of CFTR and HTR1B could help discriminate aggressive disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE46177 | GEO | 2014/12/31

SECONDARY ACCESSION(S): PRJNA197502

REPOSITORIES: GEO