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Series GSE141352 Query DataSets for GSE141352
Status Public on Nov 02, 2020
Title Effects of EGF, cetuximab, trastuzumab and afatinib on gene expression in gastric cancer cell lines
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The antibody trastuzumab in combination with platin-fluoropyrimidine chemotherapy is the standard of care for patients with HER2-positive recurrent or metastatic gastric cancer. Alternative treatment options and biomarkers for prediction of therapy response are needed since some patients do not respond to trastuzumab therapy or develop acquired resistance. We compared the molecular effects of trastuzumab and other HER-targeting drugs cetuximab and afatinib. We also tested the hypothesis that the treatment-dependent regulation of a gene indicates its importance for response, and therefore it may be used as biomarker for patient stratification. The four gastric cancer cell lines Hs746T, MKN1, MKN7 and NCI-N87 were treated with EGF, cetuximab, trastuzumab or afatinib for 4 or 24 hours. The effect on gene expression was then measured by RNA sequencing and the resulting candidate biomarkers were tested in an available cohort of gastric cancer patients or were functionally analyzed in vitro. Treatment with afatinib resulted in the highest number of regulated genes, followed by cetuximab and trastuzumab. Although trastuzumab had little effects on gene expression, we identified BMF, HAS2 and SHB as candidate biomarkers for trastuzumab response. HAS2 and SHB were confirmed as potential predictive markers for trastuzumab therapy response in clinical specimens. AREG, EREG and HBEGF were identified as candidate biomarkers for afatinib and cetuximab treatment. The functional analysis confirmed HBEGF as resistance factor for cetuximab. By confirming HAS2, SHB and HBEGF as biomarkers for anti-HER therapies, we provide evidence that the regulation of gene expression after treatment can be used for biomarker discovery.
Overall design Gastric cancer cell lines were treated with EGF, cetuximab, trastuzumab and afatinib in biological triplicates
Contributor(s) Geffers R, Ebert K, Luber B, Zwingenberger G, Arnold R, Keller S
Citation(s) 33115415, 35264144
Submission date Dec 03, 2019
Last update date Mar 31, 2022
Contact name Robert Geffers
Phone +49 531-6181-3058
Organization name HCI - Helmholtz Centre for Infection Research
Department Dep. Molecular Bacteriology
Lab Genome Analytics
Street address Inhoffenstr. 7
City Braunschweig
ZIP/Postal code 38124
Country Germany
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (132)
GSM4201677 MKN1_4h_unb_1
GSM4201678 MKN1_4h_EGF_1
GSM4201679 MKN1_4h_EGF+Cet_1
BioProject PRJNA593206
SRA SRP234536

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
GSE141352_RAW.tar 35.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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