Methylation of HOXA9 and ISL1 Predicts Patient Outcome in High-Grade Non-Invasive Bladder Cancer

PloS One
Mark O KitchenWilliam E Farrell

Abstract

Inappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in low/intermediate grade non-muscle invasive bladder cancer (NMIBC) have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG) NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin), novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis. Promoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correl...Continue Reading

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Citations

Mar 2, 2016·Epigenetics : Official Journal of the DNA Methylation Society·Mark O KitchenWilliam E Farrell
Oct 26, 2018·Current Urology Reports·Sima P Porten
Sep 8, 2020·Journal of Experimental & Clinical Cancer Research : CR·Yang JiangZhitao Jing
Dec 19, 2019·Frontiers in Genetics·Victor G MartinezJesus Maria Paramio
Oct 30, 2019·Molecular Therapy Oncolytics·Da-Fang ZhengYi-Sheng Tao

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Methods Mentioned

BETA
PCR
Assay

Software Mentioned

Excel
STATA
PyroMark Assay Design
PyroMark Q24

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