Liquid biopsies in lung cancer: Four emerging technologies and potential clinical applications

Dimple Chudasama, Periklis Katopodis, Nick Stone, Jennifer Haskell, Hannah Sheridan, Benjamin Gardner, Howard Urnovitz, Ekkehard Schuetz, Julia Beck, Marcia Hall, James Barr, Cristina Sisu, Alexandra Rice, Andreas Polychronis, Vladimir Anikin*, Emmanouil Karteris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Background: Liquid biopsies offer a promising alternative to tissue samples, providing noninvasive diagnostic approaches or serial monitoring of disease evolution. However, certain challenges remain, and the full potential of liquid biopsies has yet to be reached. Here we report several methodological approaches to interrogate liquid biopsies using circulating tumour cell (CTC) enumeration and characterisation, transcriptomics, Raman spectroscopy, and copy number instability (CNI) scores using blood samples of lung cancer (LC) patients. Methods: We choose LC; since it still is the most common cause of cancer-related mortality worldwide, and therefore there is a need for development of new non-invasive diagnostic/prognostic technologies. Changes in gene expression were assessed using RNA-seq, and in CTCs using ImageStream, an imaging flowcytometer. CNI scores, from paired tissue/ctDNA were also explored. Raman spectroscopy was used to provide chemical fingerprints of plasma samples. Results: CTCs were detected in all LC patients (n = 10). We observed a significant increase in CTC levels in LC patients (n = 10) compared to controls (n = 21). A similar CNI was noted in the tissue and plasma of 2 patients, where higher CNI scores corresponded with poorer outcome. Significant changes in Raman spectra (carotenoid concentrations) were noted in LC patients (n = 20) compared to controls (n = 10). RNA-seq revealed differential expression of 21 genes between LC cases and controls in both LC tissue and blood samples. Conclusions: Liquid biopsies can potentially provide a more comprehensive picture of the disease compared to a single tissue biopsy. CTC enumeration is feasible and sensitive for LC patients. Molecular profiling of CTCs is also possible from total blood. CNI scores and Raman spectra require further investigation. Further work is being undertaken to explore these methods of detection in a larger LC cohort.

Original languageEnglish
Article number331
JournalCancers
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 2019
Externally publishedYes

Bibliographical note

Funding Information:
Funding: This research was funded by Cancer Treatment and Research Trust (CTRT), Mount Vernon Hospital, Rickmansworth Road, Northwood, Middlesex, HA6 2RN, UK; grant number [R33209].

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Circulating tumour cells
  • Copy number instability
  • Liquid biopsies
  • Lung cancer
  • Raman Spectroscopy

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