Single tube liquid biopsy for advanced non-small cell lung cancer

Sanne de Wit, Elisabetta Rossi, Sabrina Weber, Menno Tamminga, Mariangela Manicone, Joost F. Swennenhuis, Catharina G. M. Groothuis-Oudshoorn, Riccardo Vidotto, Antonella Facchinetti, Leonie L. Zeune, Ed Schuuring, Rita Zamarchi, T. Jeroen N. Hiltermann, Michael R. Speicher, Ellen Heitzer, Leon W. M. M. Terstappen, Harry J. M. Groen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Scopus)
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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: EpCAM(high) circulating tumor cells (CTC), EpCAM(low) CTC, tumor-derived extracellular vesicles (tdEV) and cell-free circulating tumor DNA (ctDNA). EpCAM(high) CTC were detected with CellSearch, tdEV in the CellSearch images and EpCAM(low) 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 EpCAM(high) CTC, 15% had >= 2 EpCAM(low) 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 EpCAM(high) CTC and elevated levels of tdEV and ctDNA was associated with a poor OS; however, the presence of EpCAM(low) CTC was not. This single tube approach enables simultaneous analysis of multiple biomarkers to explore their potential as a liquid biopsy.

Original languageEnglish
Pages (from-to)3127-3137
Number of pages11
JournalInternational Journal of Cancer
Volume144
Issue number12
DOIs
Publication statusPublished - 15-Jun-2019

Keywords

  • liquid biopsy
  • circulating tumor cells
  • circulating tumor DNA
  • extracellular vesicles
  • survival
  • non-small cell lung cancer
  • EpCAM
  • biomarkers
  • CIRCULATING TUMOR-CELLS
  • EPITHELIAL-MESENCHYMAL PLASTICITY
  • PROGRESSION-FREE SURVIVAL
  • PROSTATE
  • PREDICT
  • CHALLENGES
  • BIOMARKERS
  • RELEVANCE
  • EXOSOMES
  • BLOOD

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