Characterization of different CTC subpopulations in non-small cell lung cancer
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Characterization of different CTC subpopulations in non-small cell lung cancer. / Hanssen, Annkathrin; Wagner, Jenny; Gorges, Tobias M; Tänzer, Aline; Uzunoglu, Faik G; Driemel, Christiane; Stoecklein, Nikolas H; Knoefel, Wolfram T; Angenendt, Sebastian; Hauch, Siegfried; Atanackovic, Djordje; Loges, Sonja; Riethdorf, Sabine; Pantel, Klaus; Wikman, Harriet.
In: SCI REP-UK, Vol. 6, 2016, p. 28010.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Characterization of different CTC subpopulations in non-small cell lung cancer
AU - Hanssen, Annkathrin
AU - Wagner, Jenny
AU - Gorges, Tobias M
AU - Tänzer, Aline
AU - Uzunoglu, Faik G
AU - Driemel, Christiane
AU - Stoecklein, Nikolas H
AU - Knoefel, Wolfram T
AU - Angenendt, Sebastian
AU - Hauch, Siegfried
AU - Atanackovic, Djordje
AU - Loges, Sonja
AU - Riethdorf, Sabine
AU - Pantel, Klaus
AU - Wikman, Harriet
PY - 2016
Y1 - 2016
N2 - Circulating tumour cells (CTCs) serve as valuable biomarkers. However, EpCAM positive CTCs are less frequently detected in NSCLC patients compared to other epithelial tumours. First, EpCAM protein expression was analysed in primary and metastatic lung cancer tissue. In both groups 21% of the samples were EpCAM negative. Second, the CellSearch system identified 15% of patients (n = 48) as CTC positive whereas a multiplex RT-PCR for PIK3CA, AKT2, TWIST, and ALDH1 following EGFR, HER2 and EpCAM based enrichment detected CTCs in 29% of the patients. Interestingly, 86% of CTC positive patients were found to express ALDH1. Only 11% of the patients were CTC-positive by both techniques. CTC positivity was associated with patient disease state when assessed by the multiplex RT-PCR assay (p = 0.015). Patients harbouring tumours with an altered EGFR genotype were more frequently CTC-positive compared to patients with EGFR wildtype tumours. In subsets of patients, CTCs were found to express genes involved in resistance to therapy such as HER3 and MET. In conclusion, using multiple targets for CTC capture and identification increases the sensitivity of CTC detection in NSCLC patients, which can be explained by the presence of different CTC subtypes with distinct molecular features.
AB - Circulating tumour cells (CTCs) serve as valuable biomarkers. However, EpCAM positive CTCs are less frequently detected in NSCLC patients compared to other epithelial tumours. First, EpCAM protein expression was analysed in primary and metastatic lung cancer tissue. In both groups 21% of the samples were EpCAM negative. Second, the CellSearch system identified 15% of patients (n = 48) as CTC positive whereas a multiplex RT-PCR for PIK3CA, AKT2, TWIST, and ALDH1 following EGFR, HER2 and EpCAM based enrichment detected CTCs in 29% of the patients. Interestingly, 86% of CTC positive patients were found to express ALDH1. Only 11% of the patients were CTC-positive by both techniques. CTC positivity was associated with patient disease state when assessed by the multiplex RT-PCR assay (p = 0.015). Patients harbouring tumours with an altered EGFR genotype were more frequently CTC-positive compared to patients with EGFR wildtype tumours. In subsets of patients, CTCs were found to express genes involved in resistance to therapy such as HER3 and MET. In conclusion, using multiple targets for CTC capture and identification increases the sensitivity of CTC detection in NSCLC patients, which can be explained by the presence of different CTC subtypes with distinct molecular features.
KW - Journal Article
U2 - 10.1038/srep28010
DO - 10.1038/srep28010
M3 - SCORING: Journal article
C2 - 27302574
VL - 6
SP - 28010
JO - SCI REP-UK
JF - SCI REP-UK
SN - 2045-2322
ER -
