Dataset Information

Epigenetic inactivation of VGF associated with Urothelial Cell Carcinoma and its potential as a non-invasive biomarker using urine.

ABSTRACT: To identify new epigenetic markers and further characterize Urothelial Cell Carcinoma (UCC), we tested the promoter methylation (PM) status of 19 genes previously identified as cancer specific methylated genes in other solid tumors.We used bisulfite sequencing, methylation specific PCR and quantitative methylation specific PCR (QMSP) to test the PM status of 19 genes in urothelial cancer cell lines.Among the 19 genes tested, VGF was found to be completely methylated in several UCC cell lines. VGF QMSP analysis showed that methylation values of almost all the primary 19 UCC tissues were higher than the paired normal tissues (P=0.009). In another cohort, 12/35 (34.3%) of low grade UCC cases displayed VGF methylation. As a biomarker for non-invasive detection of UCC, VGF showed a significantly higher frequency of methylation in urine from UCC cases (8/20) compared to controls (1/20) (P=0.020). After treatment of cell lines with 5-Aza-2'-deoxycytidine, VGF was robustly re-expressed. Forced expression of VGF in bladder cancer cell lines inhibited cell growth.Selection of candidates from genome-wide screening approach in other solid tumors successfully identified UCC specific methylated genes.

SUBMITTER: Hayashi M

PROVIDER: S-EPMC4102814 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Epigenetic inactivation of VGF associated with Urothelial Cell Carcinoma and its potential as a non-invasive biomarker using urine.

Hayashi Masamichi M Bernert Heike H Kagohara Luciane Tsukamoto LT Maldonado Leonel L Brait Mariana M Schoenberg Mark M Bivalacqua Trinity T Netto George J GJ Koch Wayne W Sidransky David D Hoque Mohammad O MO

Oncotarget 20140501 10

<h4>Background</h4>To identify new epigenetic markers and further characterize Urothelial Cell Carcinoma (UCC), we tested the promoter methylation (PM) status of 19 genes previously identified as cancer specific methylated genes in other solid tumors.<h4>Methods</h4>We used bisulfite sequencing, methylation specific PCR and quantitative methylation specific PCR (QMSP) to test the PM status of 19 genes in urothelial cancer cell lines.<h4>Results</h4>Among the 19 genes tested, VGF was found to be ...[more]

PMID: 24830820

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Project description:Background:Elucidation of epigenetic alterations in bladder cancer will lead to further understanding of the biology of the disease and hopefully improved therapies. Our aim was to perform an integrative epigenetic analysis of invasive urothelial carcinoma of the bladder to identify the epigenetic abnormalities involved in the development and progression of this cancer. Methods:Pre-processed methylation data and RNA-seq data were downloaded from The Cancer Genome Atlas (TCGA) and processed using the R package TCGA-Assembler. An R package MethylMix was used to perform an analysis incorporating both methylation and gene expression data on all samples, as well as a subset analysis comparing patients surviving less than 2 years and patients surviving more than 2 years. Genes associated with poor prognosis were individually queried. Pathway analysis was performed on statistically significant genes identified by MethylMix criteria using ConsensusPathDB. Validation was performed using flow cytometry on bladder cancer cell lines. Results:A total of 408 patients met all inclusion criteria. There were a total of 240 genes differentially methylated by MethylMix criteria. Review of individual genes specific to poor-prognosis patients revealed the majority to be candidate tumor suppressors in other cancer types. Pathway analysis showed increase in methylation of genes involved in antioxidant pathways including glutathione and NRF2. Genes involved in estrogen metabolism were also hypermethylated while genes involved in the EGFR pathway were found to be hypomethylated. EGFR expression was confirmed to be elevated in six bladder cancer cell lines. Conclusions:In patients with invasive urothelial carcinoma, we found differential methylation in patients with better and worse prognosis after cystectomy. Differentially methylated genes are involved in many relevant oncologic pathways, including EGFR and antioxidant pathways, that may be a target for therapy or chemoprevention.

Dataset Information

Epigenetic inactivation of VGF associated with Urothelial Cell Carcinoma and its potential as a non-invasive biomarker using urine.

Publications

Epigenetic inactivation of VGF associated with Urothelial Cell Carcinoma and its potential as a non-invasive biomarker using urine.

Similar Datasets

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