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Series GSE41568 Query DataSets for GSE41568
Status Public on Dec 31, 2016
Title A Molecular Profile of Colorectal Cancer to Guide Therapy [PDCCEs]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The ability to dissect heterogeneity in colorectal cancer (CRC) is a critical step in developing predictive biomarkers. The goal of this study was to develop a gene expression based molecular subgrouping model, which predicts the likelihood that patients will respond to specific therapies.

Using microarray data compiled from 848 CRC patients, we developed a subgrouping model based on 23 activated oncogenic pathway expression signatures. Stability of the model was validated in two independent data sets. To test the capacity of our model to predict patient response to specific targeted therapies and to determine the sensitivity of the subgroups to chemotherapy in vivo, we treated patient-derived colorectal cancer explants (PDCCEs) predicted to have high mTOR pathway activity with everolimus or oxaliplatin.
Results: A molecular profile of the discovery dataset revealed 8 molecular subgroups of colorectal cancer (MSCC). Both validation sets also exhibited 8 MSCC and demonstrated significant similarities to the discovery dataset. MSCC predicted to have active mTOR pathway signaling were more sensitive to everolimus compared to MSCC predicted to have low mTOR pathway activity (p=0.016). Furthermore, MSCCs displayed differential sensitivities to oxaliplatin (p<0.05).

The ability to predict oncogenic signaling pathway activation is a powerful tool that may be used to sub-classify CRCs into clinically relevant MSCCs. Patterns of pathway activation may be used to target specific therapies in CRC patients and identification of sensitivities of MSCC to specific drugs can be a powerful approach to guide therapy for CRC patients.

 
Overall design 133 (non-replicate) primary and metastatic colorectal cancer tissue samples were used in this analysis.
 
Contributor(s) Uronis JM, Hsu DS, Van Deusen JB, Proussaloglou E, Gatza ML, Datto MB, Lucas J, Barry WT, Morse MA, Mantyh C, Lyerly HK, Clary BM
Citation(s) 28060954
Submission date Oct 12, 2012
Last update date Mar 25, 2019
Contact name David Hsu
Organization name Duke University
Department Medical Oncology
Street address 905 S. LaSalle St. Rm 3008
City Durham
State/province NC
ZIP/Postal code 27710
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (133)
GSM1019390 HumanTumor_FreshFrozen_MET_CRC002D
GSM1019391 HumanTumor_FreshFrozen_MET_CRC007A
GSM1019392 HumanTumor_FreshFrozen_MET_CRC011
This SubSeries is part of SuperSeries:
GSE51244 A Molecular Profile of Colorectal Cancer to Guide Therapy
Relations
BioProject PRJNA177568

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
GSE41568_MET.PRI.normalizedMAS5JVD.txt.gz 40.2 Mb (ftp)(http) TXT
GSE41568_RAW.tar 675.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
Processed data are available on Series record

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