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Series GSE126676 Query DataSets for GSE126676
Status Public on Nov 15, 2019
Title Prognostic implications of 5-hydroxymethylcytosines from circulating cell-free DNA in diffuse large B-cell lymphoma
Organism Homo sapiens
Experiment type Methylation profiling by high throughput sequencing
Summary Elevated level of circulating cell-free DNA (cfDNA) has been associated with poor prognosis and relapse in patients with diffuse large B-cell lymphoma (DLBCL), but the tumor-specific molecular alterations in cfDNA with prognostic significance remain unclear. We investigated the association between 5-hydroxymethylcytosines (5hmC), a mark of active demethylation and gene activation, in cfDNA from blood plasma and prognosis in DLBCL. We used the 5hmC-Seal, a highly sensitive chemical labeling technique, to profile genome-wide 5hmC in plasma cfDNA samples from 48 newly diagnosed patients with DLBCL at the University of Chicago between 2010 and 2012. Patients were followed through December 31, 2017. We found a distinct genomic distribution of 5hmC in cfDNA marking tissue-specific enhancers, consistent with their potential roles in gene regulation. The 5hmC profiles in cfDNA differed by cell-of-origin, and were associated with clinical prognostic features including Ann Arbor stage, serum lactate dehydrogenase (LDH) level, and the International Prognostic Index (IPI). We developed a 29 gene-based weighted prognostic score (wp-score) for predicting event-free survival (EFS) and overall survival (OS), by applying the elastic net regularization on the Cox proportional hazard model. The wp-scores showed significantly improved prognostic accuracy and/or sensitivity/specificity than the established prognostic factors. In multivariate Cox models, patients with high wp-scores were associated with worse event-free survival (Hazard Ratio [HR] = 9.17, 95% confidence interval [CI] = 2.01- 41.89, p = 0.004), compared with those in the low risk group. Our findings suggest that the 5hmC signatures in cfDNA at the time of diagnosis are associated with clinical outcomes in DLBCL and may provide a novel non-invasive prognostic approach for DLBCL.
 
Overall design We used the 5hmC-Seal, a highly sensitive chemical labeling technique, to profile genome-wide 5hmC in plasma cfDNA samples from 48 newly diagnosed patients with DLBCL at the University of Chicago between 2010 and 2012. Patients were followed through December 31, 2017. We found a distinct genomic distribution of 5hmC in cfDNA marking tissue-specific enhancers, consistent with their potential roles in gene regulation. The 5hmC profiles in cfDNA differed by cell-of-origin, and were associated with clinical prognostic features including Ann Arbor stage, serum lactate dehydrogenase (LDH) level, and the International Prognostic Index (IPI). We developed a 29 gene-based weighted prognostic score (wp-score) for predicting event-free survival (EFS) and overall survival (OS), by applying the elastic net regularization on the Cox proportional hazard model. The wp-scores showed significantly improved prognostic accuracy and/or sensitivity/specificity than the established prognostic factors. In multivariate Cox models, patients with high wp-scores were associated with worse event-free survival (Hazard Ratio [HR] = 9.17, 95% confidence interval [CI] = 2.01- 41.89, p = 0.004), compared with those in the low risk group. Our findings suggest that the 5hmC signatures in cfDNA at the time of diagnosis are associated with clinical outcomes in DLBCL and may provide a novel non-invasive prognostic approach for DLBCL.
 
Contributor(s) Zhang W, Chiu BC, Zhang Z, You Q, Zeng C, Stepniak E, Bracci PM, Venkataraman G, He C, Smith SM
Citation(s) 31570490
Submission date Feb 17, 2019
Last update date Nov 17, 2019
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 (46)
GSM3611068 151006035_5hmC_Seal
GSM3611069 151006036_5hmC_Seal
GSM3611070 151006052_5hmC_Seal
Relations
BioProject PRJNA522918
SRA SRP186129

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
GSE126676_DLBCL_Count_Matrix.csv.gz 1.2 Mb (ftp)(http) CSV
GSE126676_Sample.Info.xlsx 13.5 Kb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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