Methylation profiling identified novel differentially methylated markers including OPCML and FLRT2 in prostate cancer

Epigenetics : Official Journal of the DNA Methylation Society
Yu WuMin Fang

Abstract

To develop new methods to distinguish indolent from aggressive prostate cancers (PCa), we utilized comprehensive high-throughput array-based relative methylation (CHARM) assay to identify differentially methylated regions (DMRs) throughout the genome, including both CpG island (CGI) and non-CGI regions in PCa patients based on Gleason grade. Initially, 26 samples, including 8 each of low [Gleason score (GS) 6] and high (GS ≥7) grade PCa samples and 10 matched normal prostate tissues, were analyzed as a discovery cohort. We identified 3,567 DMRs between normal and cancer tissues, and 913 DMRs distinguishing low from high-grade cancers. Most of these DMRs were located at CGI shores. The top 5 candidate DMRs from the low vs. high Gleason comparison, including OPCML, ELAVL2, EXT1, IRX5, and FLRT2, were validated by pyrosequencing using the discovery cohort. OPCML and FLRT2 were further validated in an independent cohort consisting of 20 low-Gleason and 33 high-Gleason tissues. We then compared patients with biochemical recurrence (n=70) vs. those without (n=86) in a third cohort, and they showed no difference in methylation at these DMR loci. When GS 3+4 cases and GS 4+3 cases were compared, OPCML-DMR methylation showed a trend of ...Continue Reading

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Citations

Sep 22, 2016·Clinical Epigenetics·Milan S GeybelsJanet L Stanford
Sep 16, 2018·Medical Oncology·Hiroki IshiharaToshikazu Ushijima
Jan 19, 2018·Science Translational Medicine·Helen R MoinovaSanford D Markowitz
Dec 18, 2018·Biomarker Research·Natalia Castaño-RodríguezNadeem O Kaakoush
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chao WangAh-Ng Kong
Nov 30, 2016·Clinical Epigenetics·René A M DirksHendrik Marks
Feb 1, 2019·Clinical and Translational Gastroenterology·Jin DaiKai-Feng Pan
Jul 1, 2020·Cancer Gene Therapy·Jane AntonyChiara Recchi
Mar 2, 2021·Frontiers in Genetics·Inês LopesJoão Pedro de Magalhães

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Methods Mentioned

BETA
methylation profiling
CHARM
Assay

Software Mentioned

CHARM
IPA
PyroMark Assay Design
R
Nexus
Ingenuity Pathway Analysis ( IPA )
Bioconductor CHARM

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