|
| Status |
Public on Apr 08, 2011 |
| Title |
Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [methylation profiling] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
|
| Summary |
The tumor microenvironment strongly influences cancer development, progression and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-beta signaling pathway. We have identified a subset of 11 genes that formed a prognostic gene expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene expression changes revealed prominent involvement of the focal adhesion and MAPK signalling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture micro-dissected corresponding primary tumor stroma compared to the matched normal lung. Six of these 14 genes could be induced by TGF-beta1 in NF. The results establish the prognostic impact of CAF-associated gene expression changes in NSCLC patients.
Methylation profiles of 5 pairs of were included in a molecular characterization of NSCLC fibroblast cell lines (CAFs) vs. normal lung fibroblasts (NFs).
|
| |
|
| Overall design |
Methylation profiles of 5 paired primary NSCLC fibroblast cell lines (CAFs) and normal lung fibroblasts (NFs) were generated. Genes were determined to be hyper- and hypo-methylated based on paired analysis.
|
| |
|
| Contributor(s) |
Navab R, Strumpf D, Tsao M |
| Citation(s) |
21474781 |
| Submission date |
Feb 14, 2011 |
| Last update date |
Jan 02, 2015 |
| Contact name |
Ming-Sound Tsao |
| E-mail(s) |
Ming.Tsao@uhn.on.ca
|
| Phone |
(416) 946-4426
|
| Organization name |
Ontario Cancer Institute/ Princess Margaret Hospital
|
| Street address |
|
| City |
Toronto |
| ZIP/Postal code |
M5G 2M9 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL8490 |
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2) |
|
| Samples (10)
|
| GSM674702 |
primary_NSCLC_fibroblast_cell_line549 |
| GSM674703 |
primary_NSCLC_fibroblast_cell_line727 |
| GSM674704 |
primary_NSCLC_fibroblast_cell_line746 |
| GSM674705 |
primary_NSCLC_fibroblast_cell_line927 |
| GSM674706 |
primary_NSCLC_fibroblast_cell_line971 |
| GSM674707 |
normal_lung_fibroblast_cell_line549 |
| GSM674708 |
normal_lung_fibroblast_cell_line727 |
| GSM674709 |
normal_lung_fibroblast_cell_line746 |
| GSM674710 |
normal_lung_fibroblast_cell_line927 |
| GSM674711 |
normal_lung_fibroblast_cell_line971 |
|
| This SubSeries is part of SuperSeries: |
| GSE22874 |
Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer |
|
| Relations |
| BioProject |
PRJNA137327 |
Less...
More...