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| Status |
Public on Jul 20, 2010 |
| Title |
Application of blood transcriptomics to identify three novel biomarkers for monitoring anti-TGFbeta therapy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Background: Development of target specific therapeutics greatly benefits from simultaneous identification of biomarkers to determine aspects of bioactivity, drug safety and efficacy or even treatment outcome. This is particularly important when targeting pleiotropic factors such as the TGFbeta system. TGFbeta has become a prime target for cancer therapeutics since inhibition of TGFbeta signaling simultaneously attacks the tumor and its microenvironment. Methods: Here we introduce blood transcriptomics followed by a defined set of validation assays as a promising approach to identify novel biomarkers for monitoring TGFbeta therapy. Findings: Our initial genome-wide analysis of transcription in peripheral blood revealed 12 candidate genes specifically regulated in peripheral blood by the TGFbeta receptor I kinase inhibitor LY2109761. In subsequent in vitro and in vivo molecular and immunological analyses, the combined monitoring of gene regulation of three genes, namely TMEPAI, OCIAD2, and SMAD7 was established as novel biomarkers for anti-TGFbeta based therapies. Interpretation: Overall, the proposed algorithm of biomarker identification is easily adapted towards other drug candidates for which gene regulation can be established in peripheral blood.
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| Overall design |
CD4+ T cells were serum-deprived for 12 hours followed by 8 hours incubation with the indicated compounds, total of 22 samples.
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| Contributor(s) |
Classen S, Muth C, Schultze J, Staratschek-Jox A |
| Citation(s) |
20084050 |
| |
| Submission date |
Mar 31, 2009 |
| Last update date |
Jan 23, 2013 |
| Contact name |
Joachim Schultze |
| E-mail(s) |
j.schultze@uni-bonn.de
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| Organization name |
LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
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| Department |
Genomics and Immunoregulation
|
| Street address |
Carl-Troll-Strasse 31
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| City |
Bonn |
| State/province |
NRW |
| ZIP/Postal code |
53115 |
| Country |
Germany |
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| Platforms (1) |
| GPL2507 |
Sentrix Human-6 Expression BeadChip |
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| Samples (22)
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| Relations |
| BioProject |
PRJNA115905 |
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