Transcriptomics,Genomics

Dataset Information

93

Expression profiling of lung cancer cell lines


ABSTRACT: Purpose: To determine the 8-week disease control rate (DCR) of sorafenib monotherapy in patients with advanced non-small-cell lung cancer (NSCLC) in the BATTLE trial. Methods: Patients with pre-treated NSCLC, ECOG performance status (PS) 0-2, consented to biopsies to test for biomarker assessment. Sorafenib was given at 400 mg orally twice daily until tumor progression or an unacceptable toxicity. Tumor evaluations were performed at baseline and every 8 weeks. Correlations of outcomes by biomarker groups were analyzed. Results: 105 patients were eligible and 98 patients were evaluable. Median age was 62 (range 34-81) years, 51% of patients were male, 75% were former/current smokers, and 89% had an ECOG PS of 0-1. Median prior chemotherapies for stage IV NSCLC were two. Median follow-up was 9.4 (range: 1.3-32.2) months. Eight-week DCRs by histology were 59.1%, 57.1%, and 55.6% for adenocarcinomas, squamous cell carcinomas and other histologies respectively. Patients with tumors harboring EGFR mutations had significantly lower 8-week DCR compared to patients with wild-type tumors (23.1% vs. 64.2%, P=0.0119), and patients with tumors harboring K-RAS mutations had the highest 8-week DCR (67%). Most commonly reported treatment-related adverse events include hand-foot syndrome (59.6%), fatigue (42.3%), rash (40.4%), diarrhea (38.5%), and weight loss (38.5%). Conclusion: 8-week DCR was better in patients treated with sorafenib who had EGFR wild-type tumors (including those with K-RAS mutations) when compared to those who had EGFR mutations. Additional analyses are warranted to further explore the biology of these tumors and related patient outcomes with sorafenib treatment. ClinicalTrials.gov number, NCT00411671. Overall design: To develop gene expression signatures for in vitro drug response and other phenotypes. To characterize human bronchial epithelial cells (HBECs) and human small airway epithelial cells (HSAECs), which are normal lung cells derived from the bronchus and peripheral areas resp. and were immortalized with CDK4 and hTERT. Expression profiling was done on 124 NSCLC and 39 SCLC cell lines, using either Illumina HumanWG-6 V3 or HumanHT-12 V4. In addition, 30 HBEC-KTs, 15 HSAEC-KTs and 14 HSAEC-UIs were profiled with Illumina HumanWG-6 V3. (KT: immortalized with CDK4 and hTERT, UI: unimmortalized)

INSTRUMENT(S): Illumina HumanWG-6 v3.0 expression beadchip

SUBMITTER: Luc Girard  

PROVIDER: GSE32036 | GEO | 2012-06-18

SECONDARY ACCESSION(S): PRJNA147685

REPOSITORIES: GEO

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Publications

An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance.

Byers Lauren Averett LA   Diao Lixia L   Wang Jing J   Saintigny Pierre P   Girard Luc L   Peyton Michael M   Shen Li L   Fan Youhong Y   Giri Uma U   Tumula Praveen K PK   Nilsson Monique B MB   Gudikote Jayanthi J   Tran Hai H   Cardnell Robert J G RJ   Bearss David J DJ   Warner Steven L SL   Foulks Jason M JM   Kanner Steven B SB   Gandhi Varsha V   Krett Nancy N   Rosen Steven T ST   Kim Edward S ES   Herbst Roy S RS   Blumenschein George R GR   Lee J Jack JJ   Lippman Scott M SM   Ang K Kian KK   Mills Gordon B GB   Hong Waun K WK   Weinstein John N JN   Wistuba Ignacio I II   Coombes Kevin R KR   Minna John D JD   Heymach John V JV  

Clinical cancer research : an official journal of the American Association for Cancer Research 20121022 1


Epithelial-mesenchymal transition (EMT) has been associated with metastatic spread and EGF receptor (EGFR) inhibitor resistance. We developed and validated a robust 76-gene EMT signature using gene expression profiles from four platforms using non-small cell lung carcinoma (NSCLC) cell lines and patients treated in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) study.We conducted an integrated gene expression, proteomic, and drug response analysis us  ...[more]

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