 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Nov 13, 2015 |
| Title |
Genome-wide DNA methylation signature in lung adenocarcinomas has prognostic impact [gene expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Purpose: DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer has in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed.
Experimental Design: We determined whole-genome DNA methylation profiles of 164 lung adenocarcinoma samples and 19 samples of matched normal lung tissue samples using the Illumina Infinium 450K array [GSE66836]. The methylation levels were correlated with gene expression levels analyzed by the Agilent 60K mRNA expression array. Methylation changes were studied specifically in tumors from never-smoking patients, and in tumors with mutations in the EGFR-, KRAS- or TP53 genes, and survival analyses were performed.
Results: We identified a large number of differentially methylated CpGs in lung adenocarcinoma tissue, and different methylation profiles in tumors from smokers and never-smokers. Specific methylation profiles were observed in tumors with mutations in the EGFR-, KRAS- or TP53 gene. Both positive and negeative correlations between DNA methylation levels and mRNA expression levels were seen. Methylation profiles of the tumor samples identified clusters of patients with distinct prognosis. A prognostic index based on the methylation levels of 33 CpGs was established, and validated in an independent cohort of lung adenocarcinoma patients from the TCGA project. Among the CpGs in the prognostic signature, some were localized in the HOX B and HOX C gene clusters.
Conclusions: Methylation differences mirror biological important features the etiology of lung adenocarcinomas and influence prognosis.
|
| |
|
| Overall design |
We determined mRNA expression in 121 lung adenocarcinoma samples using the Agilent 60K mRNA expression array. These data was correlated with the whole-genome DNA methylation profiles of matched lung adenocarcinomas to investigate the correlation of the CpG methylation to the mRNA expression. We identified a large number of both negative and positive correlations. Negative correlations between gene expression and DNA methylation were most often found when the methylated loci were located in the promoter region, while positive correlations were most often found outside promoter regions
Please note that the sample numbers are matched between the methylation study [GSE66836] and this study.
|
| |
|
| Contributor(s) |
Bjaanæs MM, Fleischer T, Halvorsen AR, Daunay A, Busato F, Solberg S, Jørgensen L, Kure E, Edvardsen H, Børresen-Dale A, Brustugun OT, Tost J, Kristensen V, Helland Å |
| Citation(s) |
26601720, 34625038, 35574381 |
| |
| Submission date |
Mar 13, 2015 |
| Last update date |
May 26, 2022 |
| Contact name |
Maria Moksnes Bjaanæs |
| E-mail(s) |
maria.moksnes.bjaanas@rr-research.no
|
| Phone |
+4797123468
|
| Organization name |
Oslo Universitetssykehus
|
| Department |
Department of genetics
|
| Street address |
Ullernchausseen 70
|
| City |
Oslo |
| ZIP/Postal code |
0310 |
| Country |
Norway |
| |
|
| Platforms (1) |
| GPL14550 |
Agilent-028004 SurePrint G3 Human GE 8x60K Microarray (Probe Name Version) |
|
| Samples (121)
|
|
| Relations |
| BioProject |
PRJNA278125 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE66863_RAW.tar |
1.4 Gb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...