Ivonne Nel1, Ulrich Jehn1, Thomas Gauler1, Andreas-Claudius Hoffmann1. 1. 1 Molecular Oncology Risk-Profile Evaluation, Department of Medical Oncology, West German Cancer Center, 2 Department of Radiotherapy, 3 Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, 45122 Essen, Germany.
Abstract
BACKGROUND: Circulating tumor cells (CTC) could serve as a "liquid biopsy" for individualizing and monitoring treatment in patients with solid tumors as recently shown by our group. We assessed which non-hematopoietic cell types are identifiable in the peripheral blood of patients with non-small cell lung cancer (NSCLC) and correlated those to clinical characteristics. METHODS: Blood from NSCLC patients (n=43) was processed as previously described. For subtype analyses CTC were negatively enriched by hematopoietic cell depletion. The remaining cell suspension included pre-enriched tumor cells and was spun onto glass slides and further characterized by multi-immunofluorescence staining against epithelial markers pan-cytokeratin (CK) and epithelial cell adhesion molecule (EpCAM), mesenchymal marker N-cadherin, stem cell marker CD133, hematopoietic marker CD45 and nuclear counterstain DAPI. Individual cell type profiles were analyzed and correlated to therapeutic outcome. RESULTS: Among other associations of CTC subtypes with clinical parameters Kaplan-Meier test revealed that an increased CD133-positive to pan-CK-positive cell type ratio (stem cell like to epithelial ratio) and the presence of mesenchymal N-cadherin+ cells, both were significantly associated to shortened PFS (2 vs. 8 months, P=0.003, HR =4.43; 5 vs. 8 months, P=0.03, HR =2.63). CONCLUSIONS: Our data suggest that different CTC populations are identifiable in peripheral blood and that these individual cell type profiles might be used to predict outcome to platinum based systemic therapies in lung cancer patients.
BACKGROUND: Circulating tumor cells (CTC) could serve as a "liquid biopsy" for individualizing and monitoring treatment in patients with solid tumors as recently shown by our group. We assessed which non-hematopoietic cell types are identifiable in the peripheral blood of patients with non-small cell lung cancer (NSCLC) and correlated those to clinical characteristics. METHODS: Blood from NSCLCpatients (n=43) was processed as previously described. For subtype analyses CTC were negatively enriched by hematopoietic cell depletion. The remaining cell suspension included pre-enriched tumor cells and was spun onto glass slides and further characterized by multi-immunofluorescence staining against epithelial markers pan-cytokeratin (CK) and epithelial cell adhesion molecule (EpCAM), mesenchymal marker N-cadherin, stem cell marker CD133, hematopoietic marker CD45 and nuclear counterstain DAPI. Individual cell type profiles were analyzed and correlated to therapeutic outcome. RESULTS: Among other associations of CTC subtypes with clinical parameters Kaplan-Meier test revealed that an increased CD133-positive to pan-CK-positive cell type ratio (stem cell like to epithelial ratio) and the presence of mesenchymal N-cadherin+ cells, both were significantly associated to shortened PFS (2 vs. 8 months, P=0.003, HR =4.43; 5 vs. 8 months, P=0.03, HR =2.63). CONCLUSIONS: Our data suggest that different CTC populations are identifiable in peripheral blood and that these individual cell type profiles might be used to predict outcome to platinum based systemic therapies in lung cancerpatients.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Andreas-Claudius Hoffmann; Peter Wild; Christina Leicht; Simone Bertz; Kathleen D Danenberg; Peter V Danenberg; Robert Stöhr; Michael Stöckle; Jan Lehmann; Martin Schuler; Arndt Hartmann Journal: Neoplasia Date: 2010-08 Impact factor: 5.715
Authors: John D O'Flaherty; Steven Gray; Derek Richard; Dean Fennell; John J O'Leary; Fiona H Blackhall; Kenneth J O'Byrne Journal: Lung Cancer Date: 2011-12-29 Impact factor: 5.705
Authors: Ivonne Nel; Hideo A Baba; Judith Ertle; Frank Weber; Barbara Sitek; Martin Eisenacher; Helmut E Meyer; Joerg F Schlaak; Andreas-Claudius Hoffmann Journal: Transl Oncol Date: 2013-08-01 Impact factor: 4.243
Authors: Jacob J Tokar; Charlotte N Stahlfeld; Jamie M Sperger; David J Niles; David J Beebe; Joshua M Lang; Jay W Warrick Journal: SLAS Technol Date: 2020-01-26 Impact factor: 3.047
Authors: Helen Schneck; Berthold Gierke; Frauke Uppenkamp; Bianca Behrens; Dieter Niederacher; Nikolas H Stoecklein; Markus F Templin; Michael Pawlak; Tanja Fehm; Hans Neubauer Journal: PLoS One Date: 2015-12-22 Impact factor: 3.240
Authors: Ivonne Nel; Thomas C Gauler; Kira Bublitz; Lazaros Lazaridis; André Goergens; Bernd Giebel; Martin Schuler; Andreas-Claudius Hoffmann Journal: PLoS One Date: 2016-04-21 Impact factor: 3.240