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Series GSE54328 Query DataSets for GSE54328
Status Public on Jan 24, 2014
Title STAG2 is a clinically relevant tumor suppressor in pancreatic ductal adenocarcinoma
Organism Homo sapiens
Experiment type Genome variation profiling by genome tiling array
Summary STAG2 is targeted by somatic aberrations in a subset (4%) of human PDAs. Transposon mediated disruption of STAG2 in a KRASG12D genetically engineered mouse model promotes the development of PDA and its progression to metastatic disease. There was a statistically significant loss of STAG2 protein expression in human tumor tissue (Wilcoxon-Rank test) with complete absence of STAG2 staining observed in 15 (4.3%) patients. In univariate Kaplan Meier analysis nearly complete STAG2 positive staining (> 95% of nuclei positive) was associated with a median survival benefit of 6.41 months (p = 0.031). The survival benefit of adjuvant chemotherapy was only seen in patients with a STAG2 staining of less than 95% (median survival benefit 7.65 months; p = 0.028). Multivariate Cox Regression analysis showed that STAG2 is an independent prognostic factor for survival in pancreatic cancer patients. Finally we show that RNAi mediated knockdown of STAG2 selectively sensitizes human PDA cell lines to platinum-based therapy.
Overall design We used DNA content flow sorting to identify and purify tumor nuclei of PDA samples from 50 patients. The genome of each sorted sample was profiled by oligonucleotide comparative genomic hybridization (aCGH) and targeted resequencing of STAG2. Transposon insertions within STAG2 in a KRASG12D driven genetically engineered mouse (GEM) model of PDA were screened by RT-PCR. We then used a tissue microarray (TMA) to survey STAG2 protein expression levels in 344 human PDA tumor samples and adjacent tissues. Univariate Kaplan Meier analysis and multivariate Cox Regression analysis was used to assess the association of STAG2 expression relative to overall survival and responses to adjuvant therapy. Finally RNAi based assays with PDA cell lines were used to assess the potential therapeutic consequence of STAG2 expression in responses to 18 therapeutic agents.
Contributor(s) Evers L, Perez-Mancera PA, Lenkiewicz E, Tang N, Aust D, Knösel T, Rümmele P, Zellweger T, Holley T, Kassner M, Aziz M, Ramanathan RK, Von Hoff D, Yin H, Pilarsky C, Barrett MT
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Submission date Jan 23, 2014
Last update date Mar 21, 2017
Contact name Michael Thomas Barrett
Phone 480-301-6736
Organization name Mayo Clinic Arizona
Department Molecular Pharmacology and Experimental Therapeutics
Street address 13400 East Shea Boulevard
City Scottsdale
State/province AZ
ZIP/Postal code 85259
Country USA
Platforms (2)
GPL4091 Agilent-014693 Human Genome CGH Microarray 244A (Feature number version)
GPL9777 Agilent-021850 SurePrint G3 Human CGH Microarray (Feature Number version)
Samples (4)
GSM1313015 12R-Pancreas-Aneuploid
GSM1313016 12R-Omentum-Aneuploid
GSM1313017 12R-Lung-Aneuploid
BioProject PRJNA236205

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
GSE54328_RAW.tar 119.5 Mb (http)(custom) TAR (of TXT)
GSE54328_UNMC12R-2N-log2ratio.txt.gz 10.7 Mb (ftp)(http) TXT
GSE54328_UNMC12R-4.5N-log2ratio.txt.gz 8.8 Mb (ftp)(http) TXT
Processed data are available on Series record

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