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Series GSE38832 Query DataSets for GSE38832
Status Public on Oct 21, 2014
Title NFAT transcriptional activity is associated with metastatic capacity in colon cancer
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Colorectal carcinoma is the third leading cause of cancer-related death in the United States. In order to understand the mechanism/signaling pathways responsible for invasion, migration and metastasis in colorectal cancer, we developed an integrative and comparative genetic approach to infer transcriptional regulatory mechanisms underlying colon cancer progression. Accordingly, we filtered fourteen human colorectal cancer (CRC) microarray data sets, from an immune competent mouse model of metastasis to identify known and novel transcriptional regulators in CRC. Using this approach, Nuclear Factor of Activated T cells (NFAT) family of transcription factors were identified as metastasis driver of colon cancer. NFAT family of transcription factors is known to induce gene transcription in various disease processes, including carcinogenesis. We used parental and metastatic derivatives of MC38 mouse colon cancer cells (MC38Par and MC38Met, respectively) to evaluate the role of NFATc1 in cancer cell invasiveness. We found that high NFATc1 expression correlates with significantly increased (p<0.0001) Trans-Endothelial Invasion (TEI) in MC38Met cells. Conversely, RNAi-based inhibition of NFATc1 expression and functional inhibition with calcineurin inhibitor FK506 in MC38Met cells, both resulted in significant decreased TEI (p=0.0193 & p=0.0003). Furthermore, a set of predicted NFATc1 target mRNAs identified in our original analysis were downregulated by knock-down of NFATc1 or functional inhibition with FK506 in MC38Met cells. The expression level (mRNA) of predicted gene targets were high in human CRC specimens which had higher than median NFATc1 mRNA expression (n=11 out of total 22). The tumor-associated NFATc1 co-regulated gene signature is significantly correlated with both disease-specific and disease-free survival in Stage II and III CRC patients. We have successfully demonstrated a bioinformatics approach to identify a tumor promoter driver gene NFATc1. Our studies suggest a role of NFATc1 towards invasion and its co-regulated gene signature for poor outcomes in colorectal cancer.
 
Overall design We developed an integrative and comparative genetic approach to infer transcriptional regulatory mechanisms underlying colon cancer progression. Using this approach, the Nuclear Factor of Activated T cells (NFAT) family of transcription factors were identified as metastasis driver of colon cancer. We used parental and metastatic derivatives of MC38 mouse colon cancer cells (MC38Par and MC38Met, respectively) to evaluate the role of NFATc1 in cancer cell invasiveness [GSE19073]. We found that high NFATc1 expression correlates with significantly increased (p<0.0001) Trans-Endothelial Invasion (TEI) in MC38Met cells. Conversely, RNAi-based inhibition of NFATc1 expression and functional inhibition with calcineurin inhibitor FK506 in MC38Met cells, both resulted in significant decreased TEI (p=0.0193 & p=0.0003). Furthermore, a set of predicted NFATc1 target mRNAs identified in our original analysis were downregulated by knock-down of NFATc1 or functional inhibition with FK506 in MC38Met cells. Finally, we generated a microarray gene expression dataset based on tumor samples collected from 122 CRC patients and tested whether the tumor-associated NFATc1co-regulated gene signature is correlated with patient survival.

The following clinical information can be found in the characteristics fields of each sample;
AJCC_STAGE: stage of cancer classified by AJCC (American Joint Committee on Cancer) staging system
DFS_EVENT: disease free survival; cancer recurrence=1, no recurrence=0
DFS_TIME: disease free survival time (months)
DSS_EVENT: disease specific survival; death from cancer=1,no death=0
DSS_TIME: disease specific survival time (months)
 
Contributor(s) Beauchamp RD, Zhang B, Chen X, Deane NG, Washington MK, Ciombor KK, Smith JJ
Citation(s) 25320007
Submission date Jun 20, 2012
Last update date Mar 25, 2019
Contact name Jing Zhu
E-mail(s) jing.zhu@vanderbilt.edu
Organization name Vanderbilt University
Street address D2300 MCN 1161 21st Ave
City Nashville
State/province TN
ZIP/Postal code 37232
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (122)
GSM950411 Patient 1
GSM950412 Patient 2
GSM950413 Patient 3
Relations
BioProject PRJNA169023

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
GSE38832_RAW.tar 591.8 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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