Abstract
The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAMhigh circulating tumor cells (CTC), EpCAMlow CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAMhigh CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAMlow CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had ≥2 EpCAMhigh CTC, 15% had ≥2 EpCAMlow CTC, 27% had ≥18 tdEV and 19% had ctDNA with ≥10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAMhigh CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAMlow CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy.
| Original language | English |
|---|---|
| Pages (from-to) | 3127-3137 |
| Number of pages | 11 |
| Journal | International journal of cancer |
| Volume | 144 |
| Issue number | 12 |
| Early online date | 11 Dec 2018 |
| DOIs | |
| Publication status | Published - 15 Jun 2019 |
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Keywords
- UT-Hybrid-D
- circulating tumor cells
- circulating tumor DNA
- EpCAM
- extracellular vesicles
- liquid biopsy
- non-small cell lung cancer
- survival
- biomarkers
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Single tube liquid biopsy for advanced non-small cell lung cancer. / de Wit, Sanne; Rossi, Elisabetta; Weber, Sabrina; Tamminga, Menno; Manicone, Mariangela; Swennenhuis, Joost F.; Groothuis-Oudshoorn, Catharina G.M.; Vidotto, Riccardo; Facchinetti, Antonella; Zeune, Leonie L.; Schuuring, Ed; Zamarchi, Rita; Hiltermann, T. Jeroen N.; Speicher, Michael R.; Heitzer, Ellen; Terstappen, Leon W.M.M.; Groen, Harry J.M. (Corresponding Author).
In: International journal of cancer, Vol. 144, No. 12, 15.06.2019, p. 3127-3137.Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Single tube liquid biopsy for advanced non-small cell lung cancer
AU - de Wit, Sanne
AU - Rossi, Elisabetta
AU - Weber, Sabrina
AU - Tamminga, Menno
AU - Manicone, Mariangela
AU - Swennenhuis, Joost F.
AU - Groothuis-Oudshoorn, Catharina G.M.
AU - Vidotto, Riccardo
AU - Facchinetti, Antonella
AU - Zeune, Leonie L.
AU - Schuuring, Ed
AU - Zamarchi, Rita
AU - Hiltermann, T. Jeroen N.
AU - Speicher, Michael R.
AU - Heitzer, Ellen
AU - Terstappen, Leon W.M.M.
AU - Groen, Harry J.M.
N1 - Wiley deal
PY - 2019/6/15
Y1 - 2019/6/15
N2 - The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAMhigh circulating tumor cells (CTC), EpCAMlow CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAMhigh CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAMlow CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had ≥2 EpCAMhigh CTC, 15% had ≥2 EpCAMlow CTC, 27% had ≥18 tdEV and 19% had ctDNA with ≥10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAMhigh CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAMlow CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy.
AB - The need for a liquid biopsy in non-small cell lung cancer (NSCLC) patients is rapidly increasing. We studied the relation between overall survival (OS) and the presence of four cancer biomarkers from a single blood draw in advanced NSCLC patients: EpCAMhigh circulating tumor cells (CTC), EpCAMlow CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAMhigh CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAMlow CTC with filtration after CellSearch. ctDNA was isolated from plasma and mutations present in the primary tumor were tracked with deep sequencing methods. In 97 patients, 21% had ≥2 EpCAMhigh CTC, 15% had ≥2 EpCAMlow CTC, 27% had ≥18 tdEV and 19% had ctDNA with ≥10% mutant allele frequency. Either one of these four biomarkers could be detected in 45% of the patients and all biomarkers were present in 2%. In 11 out of 16 patients (69%) mutations were detected in the ctDNA. Two or more unfavorable biomarkers were associated with poor OS. The presence of EpCAMhigh CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAMlow CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy.
KW - UT-Hybrid-D
KW - circulating tumor cells
KW - circulating tumor DNA
KW - EpCAM
KW - extracellular vesicles
KW - liquid biopsy
KW - non-small cell lung cancer
KW - survival
KW - biomarkers
UR - http://www.scopus.com/inward/record.url?scp=85060912389&partnerID=8YFLogxK
U2 - 10.1002/ijc.32056
DO - 10.1002/ijc.32056
M3 - Article
AN - SCOPUS:85060912389
VL - 144
SP - 3127
EP - 3137
JO - International journal of cancer
JF - International journal of cancer
SN - 0020-7136
IS - 12
ER -