Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to ...

Bredemeier, M., Edimiris, P., Mach, P., Kubista, M., Sjoback, R., Rohlova, E., Kolostova, K., Hauch, S., Aktas, B., Tewes, M., Kimmig, R., Kasimir-Bauer, S. Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to Therapy in Metastatic Breast Cancer. Clinical Chemistry, 63(10): 1585-1593, 2017. doi: 10.1373/clinchem.2016.269605. ISSN 0009-9147.

Abstract

Background

Circulating tumor cells (CTC) 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 CTC 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/StemCellSelect™ (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 CTC.

Published: 30. 5. 2018 12:22

Two-tailed RT-qPCR:… Published: 30. 5. 2018 12:23 Back to overview Horizontal transfer… Published: 30. 5. 2018 12:21