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Series GSE132118 Query DataSets for GSE132118
Status Public on May 30, 2021
Title An integrative analysis of genome-wide 5-hydroxymethylcytosines in circulating cell-free DNA detects non-invasive diagnostic markers for gliomas
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary Background. Gliomas, especially the high-grade glioblastomas (GBM), are highly aggressive tumors in the central nervous system (CNS) with dismal clinical outcomes. Effective biomarkers, which are not currently available, may improve clinical outcomes through early detection. We sought to develop a non-invasive diagnostic approach for gliomas based on 5-hydroxymethylcytosines (5hmC) in circulating cell-free DNA (cfDNA).
Methods. We obtained genome-wide 5hmC profiles using the 5hmC-Seal technique in cfDNA samples from 111 prospectively enrolled patients with gliomas and 111 age-, gender-matched healthy individuals, which were split into a training set and a validation set. Integrated models comprised of 5hmC levels summarized for gene bodies, long non-coding RNAs (lncRNAs), cis-regulatory elements, and repetitive elements were developed using the elastic net regularization under a case-control design.
Results. The integrated 5hmC-based models differentiated healthy individuals from gliomas (AUC [area under the curve] = 84%; 95% confidence interval [CI], 74-93%), GBM patients (AUC = 84%; 95% CI, 74-94%), WHO II-III glioma patients (AUC = 86%; 95% CI, 76-96%), regardless of IDH1 (encoding isocitrate dehydrogenase) mutation status or other glioma-related pathological features such as TERT, TP53 in the validation set. Furthermore, the 5hmC biomarkers in cfDNA showed the potential as an independent indicator from IDH1 mutation status and worked in synergy with IDH1 mutation to distinguish GBM from WHO II-III gliomas. Exploration of the 5hmC biomarkers for gliomas revealed relevance to glioma biology.
Conclusions. The 5hmC-Seal in cfDNA offers the promise as a non-invasive approach for effective detection of gliomas in a screening program.
 
Overall design We obtained genome-wide 5hmC profiles using the 5hmC-Seal technique in cfDNA samples from 111 prospectively enrolled patients with gliomas and 111 age-, gender-matched healthy individuals, which were split into a training set and a validation set. Integrated models comprised of 5hmC levels summarized for gene bodies, long non-coding RNAs (lncRNAs), cis-regulatory elements, and repetitive elements were developed using the elastic net regularization under a case-control design.
 
Contributor(s) Cai J, Zeng C, Hua W, Qi Z, Song Y, Lu X, Zhang Z, Zhang X, Yang Z, Zhang J, Quan K, Zhu W, Cai J, Cheng S, He C, Zhang W, Mao Y, Li D, Cui X
Citation(s) 34151267
Submission date Jun 03, 2019
Last update date Aug 30, 2021
Contact name Wei Zhang
E-mail(s) wei.zhang1@northwestern.edu
Organization name Northwestern University
Department Preventive Medicine
Street address 680 N Lake Shore Drive, Suite 1400
City Chicago
State/province IL
ZIP/Postal code 60611
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (222)
GSM3844845 SEQ3097
GSM3844846 SEQ4754
GSM3844847 SEQ3187
Relations
BioProject PRJNA545974
SRA SRP200237

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE132118_5hmC_GenebodyCount_Matrix.csv.gz 5.3 Mb (ftp)(http) CSV
GSE132118_5hmC_lncRNACount_Matrix.csv.gz 2.8 Mb (ftp)(http) CSV
GSE132118_GliomaClinicalInfo.csv.gz 1.2 Kb (ftp)(http) CSV
GSE132118_sample.info.csv.gz 4.5 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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