Methylated Genes May Become Prostate Cancer Biomarkers

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(ChemotherapyAdvisor) – Methylation of specific genes in prostate cancer may be used as diagnostic and prognostic biomarkers, according to researchers of the Mayo Clinic, Rochester, MN. This conclusion is based on a paper entitled “Global Methylation Profiling for Risk Prediction of Prostate Cancer,” which was published in Clinical Cancer Research on May 15.

In this study, the investigators aimed to determine if hypermethylation of specific gene promoters could be used diagnostically (to detect malignant prostate cells) and prognostically (to predict recurrence of disease).

DNA was isolated from prostate cancer and normal adjacent tissues and then the methylation state of 14,495 genes was determined by a microarray analysis. Methylation profiles were analyzed in 4 different groups: group 1 compared tumor (n=198) vs. matched normal tissues (n=40); group 2 compared recurrence (n=123) vs. non-recurrence (n=75); group 3 compared clinical recurrence (n=80) vs. biochemical recurrence (n=43); and group 4 compared systemic recurrence (n=36) vs. local recurrence (n=44).

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 groups 1, 2, and 4, 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.

The investigators concluded: “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.”

Abstract

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