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Series GSE148766 Query DataSets for GSE148766
Status Public on Apr 15, 2021
Title Prognostic epigenetic 12-genes signature in human metastatic colorectal carcinomas
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Epigenetic remodeling is responsible for tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that DNA methylation profiling may identify metastatic CRC (mCRC) subtypes with defined clinical characters. Global differential methylation profile was comparatively analyzed between 24 first-line primary-resistant and 12 drug-sensitive mCRCs, two subgroups with significantly different outcome. Gene expression and methylation data from the TCGA mCRCs cohort were used to identify, among differentially methylated genes, a prognostic signature of functionally methylated genes. Twelve functionally methylated genes yielded a hierarchical clustering of patients in two well-defined subgroups with hypermethylated tumors characterized by a significantly worst relapse-free and overall survival compared to hypomethylated cancers. Interestingly, the poor prognosis cluster was enriched of CIMP-high and MSI-like cases. Furthermore, methylation events were enriched in genes located on arms q of chromosomes 13 and 20, this suggesting that epigenetic remodeling may involve selective genomic regions. Finally, the expression of the 12-genes signature and MSI-enriching genes was confirmed in two independent oxaliplatin- and irinotecan-resistant CRC cell lines. These data provide the proof of concept that the hypermethylation of specific sets of genes may provide prognostic informations being able to identify a subgroup of mCRCs with poor prognosis
 
Overall design Bisulphite converted DNA from the 36 samples were hybridized to the Illumina Infinium 850K Human Methylation Beadchip v1.2
Web link https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13010158
 
Contributor(s) Condelli V, Calice G
Citation(s) 33466447, 35953834
Submission date Apr 16, 2020
Last update date Aug 24, 2022
Contact name Valentina Condelli
E-mail(s) valentina.condelli@crob.it
Organization name IRCCS CROB
Street address Via Padre Pio, 1
City Rionero in Vulture
State/province PZ
ZIP/Postal code 85028
Country Italy
 
Platforms (1)
GPL21145 Infinium MethylationEPIC
Samples (36)
GSM4478634 FFPE colorectal cancer sample, OHP-sens 1
GSM4478635 FFPE colorectal cancer sample, OHP-sens 2
GSM4478636 FFPE colorectal cancer sample, OHP-sens 3
Relations
BioProject PRJNA625692

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
GSE148766_RAW.tar 161.2 Mb (http)(custom) TAR
GSE148766_matrix_signal_Unmeth_Meth_DetPval_FOLFIRI.txt.gz 78.7 Mb (ftp)(http) TXT
GSE148766_matrix_signal_Unmeth_Meth_DetPval_FOLFOX.txt.gz 92.6 Mb (ftp)(http) TXT
Processed data included within Sample table
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