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Series GSE34138 Query DataSets for GSE34138
Status Public on Dec 01, 2012
Title SERPINA6, BEX1, AGTR1, SLC26A3, and LAPTM4B are markers of resistance to neoadjuvant chemotherapy in HER2-negative breast cancer
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Abstract

Introduction
Response rates to chemotherapy remain highly variable in breast cancer patients. We set out to identify genes associated with chemotherapy resistance. We analyzed what is currently the largest single-institute set of gene expression profiles derived from breast cancers prior to a single neoadjuvant chemotherapy regimen (dose-dense doxorubicine and cyclophophamide).
Methods
We collected, gene expression-profiled and analyzed 178 HER2-negative breast tumor biopsies (‘NKI dataset’). We employed a recently developed approach for detecting imbalanced differential signal (DIDS) in order to identify markers of resistance to treatment. In contrast to traditional methods, DIDS is able to identify markers that show aberrant expression in only a small subgroup of the non-responder samples.
Results
We found a number of markers of resistance to anthracycline-based chemotherapy. We validated our findings by the analysis of three external datasets, which contained 456 HER2-negative samples in total. Since these external sets included patients who received differing treatment regimens we could only validate markers of general chemotherapy resistance. There was a highly significant overlap in the markers identified in the NKI dataset and the other three datasets. Five resistance markers, SERPINA6, BEX1, AGTR1, SLC26A3, and LAPTM4B, were identified in three of the four datasets (p-value overlap <1e-6). These five genes identified resistant tumors that could not have been identified by merely taking ER-status or proliferation into account.
Conclusion
The identification of these genes might lead to a better understanding of the mechanisms involved in (clinically) observed chemotherapy resistance and could possibly assist in the recognition of breast cancers in which chemotherapy does not contribute to response or survival.
 
Overall design We collected, gene expression profiled and analyzed 178 HER2-negative breast tumor biopsies, obtained from patients scheduled to undergo neoadjuvant therapy.
 
Contributor(s) de Ronde JJ, Lips E, Mulder L, Vincent A, Wesseling J, Nieuwland M, Kerkhoven R, Vrancken Peeters MT, Sonke GS, Rodenhuis S, Wessels LF
Citation(s) 23203637, 28919995
Submission date Dec 05, 2011
Last update date Jun 26, 2019
Contact name Jelle Johannes ten Hoeve
E-mail(s) j.t.hoeve@nki.nl
Organization name Netherlands Cancer Institute
Department Molecular Biology
Lab Bioinformatics and Statistics
Street address Plesmanlaan 121
City Amsterdam
ZIP/Postal code 1066 CX
Country Netherlands
 
Platforms (1)
GPL6884 Illumina HumanWG-6 v3.0 expression beadchip
Samples (178)
GSM842290 PR+NR breast cancer BC_4531933092_C
GSM842291 PR+NR breast cancer BC_4531933092_D
GSM842292 PR+NR breast cancer BC_4531933092_E
Relations
BioProject PRJNA150065

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
GSE34138_RAW.tar 6.3 Mb (http)(custom) TAR
GSE34138_non-normalized.txt.gz 44.2 Mb (ftp)(http) TXT
Processed data included within Sample table
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