In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 109-109
Abstract:
DNA methylation profiles could signify the risk of prostate cancer and predict the progression of cancer before the appearance of clinical symptoms. Specific CpG sites methylation of genes identified in our study could be used to improve the sensitivity and specificity for early diagnosis and to predict the risk of prostate cancer recurrence. To identify methylation changes associated with prostate cancer, we measured gene methylation using the Infinium Human Methylation27 bead chips. Tissue DNA isolation and bisulfite conversion was done using ZR Genomic DNA kit and EZ methylation kit. The methylation27 microarrays was used to analyze methylation of 27,578 CpG sites of 14,495 genes in 198 tumor tissues and 40 matched normal tissues. Methylation data was processed using the Genome Studio software, differentially methylated genes identified using one-way analysis of variance, and correction for multiple testing done using the false discovery rate q-value. To identify putative diagnostic and prognostic biomarkers we performed four subgroup comparisons: tumor vs. matched normal, recurrent tumors vs. non-recurrent tumors, clinical recurrence vs. biochemical recurrence, and systemic recurrence vs. local recurrence. Clinicopathological and molecular features including patient preoperative PSA levels, Gelason score, TNM stage, GPSM, recurrence type, were also evaluated for subgroup discrimination. Discriminative subgroup candidate methlyation markers were selected using a p value & lt;0.05 and a mean difference between two contrast groups & gt;0.05. Between the tumor and matched normal tissue samples, 164 CpG sites representing 147 genes were identified as significantly differentially methylated (p & lt;9.99E-25, fold change & gt;2.0). Between recurrent tumor and non-recurrent tumor tissues there were 78 CpG sites representing 75 genes that were significantly differentially methylated (p & lt;0.002, fold change & gt;1.5). Between clinically recurrent and biochemically recurrent tumors, 16 CpG sites representing 16 genes were significantly differentially methylated (p & lt;0.05, fold change & gt;1.5). Between systemic recurrent and local recurrent tumors there were 73 CpG sites representing 68 genes that were significantly differentially methylated (p & lt;0.01, fold change & gt;1.5) Our analysis revealed differential methylation of the genes, implicating their role in prostate cancer development and progression. We demonstrated that the hypermethylation of genes could be used as a sensitive molecular tool in detection of prostate tumorigenesis and prediction of tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 109. doi:10.1158/1538-7445.AM2011-109
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-109
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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