Global methylation profiling for risk prediction of prostate cancer

Saswati Mahapatra, Eric W Klee, Charles Y F Young, Zhifu D Sun, Rafael E Jimenez, George G. Klee, Donald J. Tindall, Krishna Vanaja Donkena

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Purpose: The aim of this study was to investigate the promoter hypermethylation as diagnostic markers to detect malignant prostate cells and as prognostic markers to predict the clinical recurrence of prostate cancer. Experimental Design:DNAwas isolated from prostate cancer and normal adjacent tissues. After bisulfite conversion, methylation of 14,495 genes was evaluated using the Methylation27 microarrays in 238 prostate tissues. We analyzed methylation profiles in four different groups: (i) tumor (n = 198) versus matched normal tissues (n = 40), (ii) recurrence (n = 123) versus nonrecurrence (n = 75), (iii) clinical recurrence (n = 80) versus biochemical recurrence (n = 43), and (iv) systemic recurrence (n = 36) versus local recurrence (n = 44). Group 1, 2, 3, and 4 genes signifying biomarkers for diagnosis, prediction of recurrence, clinical recurrence, and systemic progression were determined. Univariate and multivariate analyses were conducted to predict risk of recurrence. We validated the methylation of genes in 20 independent tissues representing each group by pyrosequencing. Results: Microarray analysis revealed significant methylation of genes in four different groups of prostate cancer tissues. The sensitivity and specificity of methylation for 25 genes from 1, 2, and 4 groups and 7 from group 3 were shown. Validation of genes by pyrosequencing from group 1 (GSTP1, HIF3A, HAAO, and RARβ), group 2 (CRIP1, FLNC, RASGRF2, RUNX3, and HS3ST2), group 3 (PHLDA3, RASGRF2, and TNFRSF10D), and group 4 (BCL11B, POU3F3, and RASGRF2) confirmed the microarray results. Conclusions: Our study provides a global assessment of DNA methylation in prostate cancer and identifies the significance of genes as diagnostic and progression biomarkers of prostate cancer.

Original languageEnglish (US)
Pages (from-to)2882-2895
Number of pages14
JournalClinical Cancer Research
Volume18
Issue number10
DOIs
StatePublished - May 15 2012

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Methylation
Prostatic Neoplasms
Recurrence
Genes
Prostate
Biomarkers
DNA Methylation
Microarray Analysis
Research Design
Multivariate Analysis
Sensitivity and Specificity
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Global methylation profiling for risk prediction of prostate cancer. / Mahapatra, Saswati; Klee, Eric W; Young, Charles Y F; Sun, Zhifu D; Jimenez, Rafael E; Klee, George G.; Tindall, Donald J.; Donkena, Krishna Vanaja.

In: Clinical Cancer Research, Vol. 18, No. 10, 15.05.2012, p. 2882-2895.

Research output: Contribution to journalArticle

Mahapatra, Saswati ; Klee, Eric W ; Young, Charles Y F ; Sun, Zhifu D ; Jimenez, Rafael E ; Klee, George G. ; Tindall, Donald J. ; Donkena, Krishna Vanaja. / Global methylation profiling for risk prediction of prostate cancer. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 10. pp. 2882-2895.
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abstract = "Purpose: The aim of this study was to investigate the promoter hypermethylation as diagnostic markers to detect malignant prostate cells and as prognostic markers to predict the clinical recurrence of prostate cancer. Experimental Design:DNAwas isolated from prostate cancer and normal adjacent tissues. After bisulfite conversion, methylation of 14,495 genes was evaluated using the Methylation27 microarrays in 238 prostate tissues. We analyzed methylation profiles in four different groups: (i) tumor (n = 198) versus matched normal tissues (n = 40), (ii) recurrence (n = 123) versus nonrecurrence (n = 75), (iii) clinical recurrence (n = 80) versus biochemical recurrence (n = 43), and (iv) systemic recurrence (n = 36) versus local recurrence (n = 44). Group 1, 2, 3, and 4 genes signifying biomarkers for diagnosis, prediction of recurrence, clinical recurrence, and systemic progression were determined. Univariate and multivariate analyses were conducted to predict risk of recurrence. We validated the methylation of genes in 20 independent tissues representing each group by pyrosequencing. Results: Microarray analysis revealed significant methylation of genes in four different groups of prostate cancer tissues. The sensitivity and specificity of methylation for 25 genes from 1, 2, and 4 groups and 7 from group 3 were shown. Validation of genes by pyrosequencing from group 1 (GSTP1, HIF3A, HAAO, and RARβ), group 2 (CRIP1, FLNC, RASGRF2, RUNX3, and HS3ST2), group 3 (PHLDA3, RASGRF2, and TNFRSF10D), and group 4 (BCL11B, POU3F3, and RASGRF2) confirmed the microarray results. Conclusions: Our study provides a global assessment of DNA methylation in prostate cancer and identifies the significance of genes as diagnostic and progression biomarkers of prostate cancer.",
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AU - Klee, George G.

AU - Tindall, Donald J.

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