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Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to Therapy in Metastatic Breast Cancer
M. Bredemeier, P. Edimiris, P. Mach, M. Kubista, R. Sjöback, E. Rohlova, K. Kolostova, S. Hauch, B. Aktas, M. Tewes, R. Kimmig, S. Kasimir-Bauer,
Language English Country United States
Document type Journal Article
NLK
ProQuest Central
from 2002-12-01 to 2022-04-30
Open Access Digital Library
from 1955-02-01
Medline Complete (EBSCOhost)
from 2010-01-01 to 1 year ago
Nursing & Allied Health Database (ProQuest)
from 2002-12-01 to 2022-04-30
Health & Medicine (ProQuest)
from 2002-12-01 to 2022-04-30
Public Health Database (ProQuest)
from 2002-12-01 to 2022-04-30
- MeSH
- Humans MeSH
- Biomarkers, Tumor genetics MeSH
- Neoplastic Cells, Circulating metabolism pathology MeSH
- Breast Neoplasms blood diagnosis genetics therapy MeSH
- Prognosis MeSH
- ADAM17 Protein genetics MeSH
- Breast pathology MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Transcriptome * MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Circulating tumor cells (CTCs) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTCs of MBC patients on the basis of the expression of 46 genes. METHODS: From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest EMT-2/StemCellSelectTM (QIAGEN). Patients were grouped into (a) responder (R) and non-responder (NR) at TP1 and (b) overall responder (OR) and overall non-responder (ONR) at TP2. A 46-gene PCR assay was used for preamplification and high-throughput gene expression profiling. Data were analyzed by use of GenEx (MultiD) and SAS. RESULTS: The CTC positivity was defined by the four-gene signature (EPCAM, KRT19, MUC1, ERBB2 positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC- patients (KRT19, FLT1, EGFR, EPCAM, GZMM, PGR, CD24, KIT, PLAU, ALDH1A1, CTSD, MKI67, TWIST1, and ERBB2). KRT19 was highly expressed in CTC+ patients and ADAM17 in the NR at TP1. A significant differential expression of 4 genes (KRT19, EPCAM, CDH1, and SCGB2A2) was observed between OR and ONR when stratifying the samples into CTC+ or CTC-. CONCLUSIONS: ADAM17 could be a key marker in distinguishing R from NR, and KRT19 was powerful in identifying CTCs.
Department of Gynecology and Obstetrics University Hospital Essen Essen Germany
Department of Laboratory Genetics University Hospital Kralovske Vinohrady Prague Czech Republic
Department of Medical Oncology West German Cancer Center University Hospital Essen Essen Germany
TATAA Biocenter Goeteborg Sweden
TATAA Biocenter Goeteborg Sweden Institute of Biotechnology CAS Prague Czech Republic
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- $a BACKGROUND: Circulating tumor cells (CTCs) are thought to be an ideal surrogate marker to monitor disease progression in metastatic breast cancer (MBC). We investigated the prediction of treatment response in CTCs of MBC patients on the basis of the expression of 46 genes. METHODS: From 45 MBC patients and 20 healthy donors (HD), 2 × 5 mL of blood was collected at the time of disease progression (TP0) and at 2 consecutive clinical staging time points (TP1 and TP2) to proceed with the AdnaTest EMT-2/StemCellSelectTM (QIAGEN). Patients were grouped into (a) responder (R) and non-responder (NR) at TP1 and (b) overall responder (OR) and overall non-responder (ONR) at TP2. A 46-gene PCR assay was used for preamplification and high-throughput gene expression profiling. Data were analyzed by use of GenEx (MultiD) and SAS. RESULTS: The CTC positivity was defined by the four-gene signature (EPCAM, KRT19, MUC1, ERBB2 positivity). Fourteen genes were identified as significantly differentially expressed between CTC+ and CTC- patients (KRT19, FLT1, EGFR, EPCAM, GZMM, PGR, CD24, KIT, PLAU, ALDH1A1, CTSD, MKI67, TWIST1, and ERBB2). KRT19 was highly expressed in CTC+ patients and ADAM17 in the NR at TP1. A significant differential expression of 4 genes (KRT19, EPCAM, CDH1, and SCGB2A2) was observed between OR and ONR when stratifying the samples into CTC+ or CTC-. CONCLUSIONS: ADAM17 could be a key marker in distinguishing R from NR, and KRT19 was powerful in identifying CTCs.
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