Maren Bredemeier1, Philippos Edimiris1, Pawel Mach1, Mikael Kubista2,3, Robert Sjöback2, Eva Rohlova2, Katarina Kolostova4, Siegfried Hauch5, Bahriye Aktas1, Mitra Tewes6, Rainer Kimmig1, Sabine Kasimir-Bauer7. 1. Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany. 2. TATAA Biocenter, Goeteborg, Sweden. 3. Institute of Biotechnology CAS, Prague, Czech Republic. 4. Department of Laboratory Genetics, University Hospital Kralovske Vinohrady, Prague, Czech Republic. 5. QIAGEN GmbH, Hilden, Germany. 6. Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany. 7. Department of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany; sabine.kasimir-bauer@uk-essen.de.
Abstract
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.
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 MBCpatients on the basis of the expression of 46 genes. METHODS: From 45 MBCpatients 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.
Authors: Pradyumna Kedarisetti; Vincent R Bouvet; Wei Shi; Cody N Bergman; Jennifer Dufour; Afshin Kashani Ilkhechi; Kevan L Bell; Robert J Paproski; John D Lewis; Frank R Wuest; Roger J Zemp Journal: Biomed Opt Express Date: 2020-10-08 Impact factor: 3.732
Authors: Dan Georgess; Veena Padmanaban; Orit Katarina Sirka; Kester Coutinho; Alex Choi; Gabriela Frid; Neil M Neumann; Takanari Inoue; Andrew J Ewald Journal: Cancer Res Date: 2019-11-01 Impact factor: 12.701